ABSTRACT
Drug addiction therapies commonly fail because continued drug use promotes the release of excessive and pleasurable dopamine levels. Because the connection between pleasure and drug use becomes hard-wired in the nucleus accumbens (NAc), which interfaces motivation, effective therapies need to modulate this mesolimbic reward system. Here, we report that mice with knockdown of the cation channel TRPA1 (transient receptor potential ankyrin 1) were resistant to the drug-seeking behavior and reward effects of cocaine compared to their wildtype litter mates. In our study, we demonstrate that TRPA1 inhibition in the NAc reduces cocaine activity and dopamine release, and conversely, that TRPA1 is critical for cocaine-induced synaptic strength in dopamine receptor 1-expressing medium spiny neurons. Taken together, our data support that cocaine-induced reward-related behavior and synaptic release of dopamine in the NAc are controlled by TRPA1 and suggest that TRPA1 has therapeutic potential as a target for drug misuse therapies.
ABSTRACT
The selenium-binding protein 1 (SELENBP1) has been reported to be up-regulated in the prefrontal cortex (PFC) of schizophrenia patients in postmortem reports. However, no causative link between SELENBP1 and schizophrenia has yet been established. Here, we provide evidence linking the upregulation of SELENBP1 in the PFC of mice with the negative symptoms of schizophrenia. We verified the levels of SELENBP1 transcripts in postmortem PFC brain tissues from patients with schizophrenia and matched healthy controls. We also generated transgenic mice expressing human SELENBP1 (hSELENBP1 Tg) and examined their neuropathological features, intrinsic firing properties of PFC 2/3-layer pyramidal neurons, and frontal cortex (FC) electroencephalographic (EEG) responses to auditory stimuli. Schizophrenia-like behaviors in hSELENBP1 Tg mice and mice expressing Selenbp1 in the FC were assessed. SELENBP1 transcript levels were higher in the brains of patients with schizophrenia than in those of matched healthy controls. The hSELENBP1 Tg mice displayed negative endophenotype behaviors, including heterotopias- and ectopias-like anatomical deformities in upper-layer cortical neurons and social withdrawal, deficits in nesting, and anhedonia-like behavior. Additionally, hSELENBP1 Tg mice exhibited reduced excitabilities of PFC 2/3-layer pyramidal neurons and abnormalities in EEG biomarkers observed in schizophrenia. Furthermore, mice overexpressing Selenbp1 in FC showed deficits in sociability. These results suggest that upregulation of SELENBP1 in the PFC causes asociality, a negative symptom of schizophrenia.
Subject(s)
Schizophrenia , Humans , Animals , Mice , Schizophrenia/genetics , Schizophrenia/metabolism , Prefrontal Cortex/metabolism , Pyramidal Cells/metabolism , Brain/metabolism , Mice, Transgenic , Selenium-Binding Proteins/genetics , Selenium-Binding Proteins/metabolismABSTRACT
The medial prefrontal cortex (mPFC) has been implicated in regulating resistance to the effects of acute uncontrollable stress. We previously showed that mPFC-lesioned animals exhibit impaired object recognition memory after acute exposure to a brief stress that had no effect in normal animals. Here, we used designer receptors exclusively activated by designer drugs to determine how modulating mPFC activity affects recognition-memory performance under stressful conditions. Specifically, animals with chemogenetic excitation or inhibition of the mPFC underwent either a brief ineffective stress (20-min restraint + 20 tail shocks) or a prolonged effective stress (60-min restraint + 60 tail shocks). Subsequent recognition memory tests showed that animals with chemogenetic mPFC inhibition exposed to brief stress showed impairment in an object recognition memory task, whereas those with chemogenetic mPFC excitation exposed to prolonged stress did not. Thus, the present findings the decreased mPFC activity exacerbates acute stress effects on memory function whereas increased mPFC activity counters these stress effects provide evidence that the mPFC bidirectionally modulates stress resistance.
Subject(s)
Cognitive Dysfunction , Memory , Prefrontal Cortex , Recognition, Psychology , Stress, Physiological , Stress, Psychological , Animals , Male , Rats , Clozapine/analogs & derivatives , Clozapine/pharmacology , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/prevention & control , Electroshock/psychology , Memory/drug effects , Memory/physiology , Prefrontal Cortex/drug effects , Prefrontal Cortex/physiology , Rats, Sprague-Dawley , Recognition, Psychology/drug effects , Recognition, Psychology/physiology , Restraint, Physical/physiology , Stress, Physiological/physiology , Stress, Psychological/complications , Stress, Psychological/physiopathology , Time FactorsABSTRACT
Ventriculoperitoneal shunt surgery was developed to manage excessive cerebrospinal fluid (CSF) in the brain's ventricles and is considered a mainstream treatment. Despite the development of the shunt device system, various complications still occur. In this study, we reported 307 cases and a long-term follow-up of at least five years of adult patients who underwent VP shunt surgery and analyzed various factors that may affect revision surgery. A retrospective study was conducted at Asan Medical Center, Korea, a tertiary medical center. We reviewed 307 cases from January 2012 to December 2018. The patients' neurological status, predisposing medical conditions, laboratory findings, and other operation-related factors were reviewed using electrical medical records. The normal function group comprised 272 cases (88.6%), and the overall incidence of revision group comprised 35 cases (11.4%). Of the 35 revision surgery cases, 30 (85.71%) were due to shunt malfunctions, such as obstruction, overdrainage, and valve-related errors while 5 (14.29%) were due to shunt infection. Patient demographics, mental status, and operation time did not influence revision as risk factors. Serum laboratory findings showed no statistical difference between the two groups. The white blood cell (WBC) count in the CSF profile differed significantly between the two groups. The Hakim Programmable valve (Codman, USA) is mainly used in our center. In addition, various shunt systems were used, including Strata Regulatory valve (Medtronic, USA), proGAV (Aesculap, USA), and Accu-Flo (Codman, USA). This study analyzed the factors affecting long-term outcomes. Based on these findings, efforts are needed to achieve more favorable outcomes in the future.
Subject(s)
Hydrocephalus , Ventriculoperitoneal Shunt , Humans , Ventriculoperitoneal Shunt/adverse effects , Male , Female , Middle Aged , Risk Factors , Adult , Retrospective Studies , Incidence , Aged , Follow-Up Studies , Hydrocephalus/surgery , Reoperation , Postoperative Complications/epidemiology , Equipment Failure , Young AdultABSTRACT
BACKGROUND: Liver transplantation (LT) patients appear to be more prone to neurological events compared to individuals undergoing other types of solid-organ transplantation. The aims of the present study were to analyze the prevalence of unruptured intracranial aneurysms (UIAs) in patients undergoing liver transplantation (LT) and to examine the perioperative occurrence of subarachnoid hemorrhage (SAH). Also, it intended to systematically identify the risk factors of SAH and hemorrhagic stroke (HS) within a year after LT and to develop a scoring system which involves distinct clinical features of LT patients. METHODS: Patients who underwent LT from January 2012 to March 2022 were analyzed. All included patients underwent neurovascular imaging within 6 months before LT. We conducted an analysis of prevalence and radiological features of UIA and SAH. The clinical factors that may have an impact on HS within one year of LT were also reviewed. RESULTS: Total of 3,487 patients were enrolled in our study after applying inclusion and exclusion criteria. The prevalence of UIA was 5.4%. The incidence of SAH and HS within one year following LT was 0.5% and 1.6%, respectively. We developed a scoring system based on multivariable analysis to predict the HS within 1-year after LT. The variables were a poor admission mental status, the diagnosis of UIA, serum ammonia levels, and Model for End-stage Liver Disease (MELD) scores. Our model showed good discrimination among the development (C index, 0.727; 95% confidence interval [CI], 0.635-0.820) and validation (C index, 0.719; 95% CI, 0.598-0.801) cohorts. CONCLUSION: The incidence of UIA and SAH was very low in LT patients. A poor admission mental status, diagnosis of UIA, serum ammonia levels, and MELD scores were significantly associated with the risk of HS within one year after LT. Our scoring system showed a good discrimination to predict the HS in LT patients.
Subject(s)
End Stage Liver Disease , Hemorrhagic Stroke , Intracranial Aneurysm , Liver Transplantation , Stroke , Subarachnoid Hemorrhage , Humans , Intracranial Aneurysm/diagnosis , Intracranial Aneurysm/epidemiology , Intracranial Aneurysm/surgery , Hemorrhagic Stroke/complications , Liver Transplantation/adverse effects , Ammonia , End Stage Liver Disease/complications , Severity of Illness Index , Subarachnoid Hemorrhage/diagnosis , Subarachnoid Hemorrhage/epidemiology , Subarachnoid Hemorrhage/etiology , Stroke/diagnosis , Stroke/epidemiology , Stroke/etiologyABSTRACT
PURPOSE: An anterior communicating artery is a common location for both ruptured and unruptured intracranial aneurysms, and microsurgery is sometimes necessary for their successful treatment. However, postoperative infarction should be considered during clipping due to the complex surrounding structures of anterior communicating artery aneurysms. This study aimed to evaluate the risk factors of postoperative infarction after surgical clipping of unruptured anterior communicating artery aneurysms and its clinical outcomes. METHODS: The data of patients who underwent microsurgical clipping of an unruptured anterior communicating artery aneurysm in our hospital between January 2008 and December 2020 were retrospectively analyzed. The patients' demographic data, anatomical features of the anterior communicating artery complex and aneurysm, surgical technique, characteristics of postoperative infarction, and its clinical course were evaluated. RESULTS: Notably, among 848 patients, 66 (7.8%) and 34 (4%) patients had radiologic and symptomatic infarctions, respectively. Univariate and multivariate logistic regression analyses showed that hypertension (odds ratio (OR), 1.99; [Formula: see text]), previous stroke (OR, 3.89; [Formula: see text]), posterior projection (OR, 5.58; [Formula: see text]), aneurysm size (OR, 1.17; optimal cut-off value, 6.14 mm; [Formula: see text]), and skull base-to-aneurysm distance (OR, 1.15; optimal cut-off value, 11.09 mm; [Formula: see text]) were associated with postoperative infarction. In the pterional approach, a closed A2 plane was an additional risk factor (OR, 1.88; [Formula: see text]). Infarction of the subcallosal and hypothalamic branches was significantly associated with symptomatic infarction ([Formula: see text]). CONCLUSION: Hypertension, previous stroke, posteriorly projecting aneurysms, aneurysm size, and highly positioned aneurysms are independent risk factors for postoperative infarction during surgical clipping of an unruptured anterior communicating artery aneurysm. Additionally, a closed A2 plane is an additional risk factor of postoperative infarction in patients undergoing clipping via the pterional approach.
Subject(s)
Aneurysm, Ruptured , Intracranial Aneurysm , Stroke , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Intracranial Aneurysm/complications , Retrospective Studies , Infarction/complications , Risk Factors , Stroke/complications , Aneurysm, Ruptured/diagnostic imaging , Aneurysm, Ruptured/surgery , Aneurysm, Ruptured/complications , Treatment OutcomeABSTRACT
BACKGROUND: Subarachnoid hemorrhage (SAH) patients have oxidative stress results in inflammation, tissue degeneration and neuronal damage. These deleterious effects cause aggravation of the perihematomal edema (PHE), vasospasm, and even hydrocephalus. We hypothesized that antioxidants may have a neuroprotective role in acute aneurysmal SAH (aSAH) patients. METHODS: We conducted a prospective, multicenter randomized (single blind) trial between January 2017 and October 2019, investigating whether antioxidants (acetylcysteine and selenium) have the potential to improve the neurologic outcome in aSAH patients. The antioxidant patient group received antioxidants of acetylcysteine (2,000 mg/day) and selenium (1,600 µg/day) intravenously (IV) for 14 days. These drugs were administrated within 24 hours of admission. The non-antioxidant patient group received a placebo IV. RESULTS: In total, 293 patients were enrolled with 103 patients remaining after applying the inclusion and exclusion criteria. No significant differences were observed in the baseline characteristics between the antioxidant (n = 53) and non-antioxidant (n = 50) groups. Among clinical factors, the duration of intensive care unit (ICU) stay was significantly shortened in patients who received antioxidants (11.2, 95% confidence interval [CI], 9.7-14.5 vs. 8.3, 95% CI, 6.2-10.2 days, P = 0.008). However, no beneficial effects were observed on radiological outcomes. CONCLUSION: In conclusion, antioxidant treatment failed to show the reduction of PHE volume, mid-line shifting, vasospasm and hydrocephalus in acute SAH patients. A significant reduction in ICU stay was observed but need more optimal dosing schedule and precise outcome targets are required to clarify the clinical impacts of antioxidants in these patients. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0004628.
Subject(s)
Hydrocephalus , Selenium , Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/drug therapy , Acetylcysteine/therapeutic use , Selenium/therapeutic use , Prospective Studies , Single-Blind Method , Treatment Outcome , Hydrocephalus/etiology , Hydrocephalus/complicationsABSTRACT
Posterior communicating artery (PCoA) aneurysm is common and sometimes requires microsurgery; however, as data on premammillary artery (PMA) infarction after clipping is scarce, we retrospectively reviewed cases of post-clipping PMA infarction to analyze incidence, independent risk factors of infarction, and anatomical considerations. Data from 569 consecutive patients who underwent microsurgical clipping for unruptured PCoA aneurysm between January 2008 and December 2020 were included. Patients were categorized into the normal or the PMA infarction group. Statistical analyses and comparisons between the two groups were used to determine the influence of various factors. The normal group included 515 patients while the PMA infarction group had 31. The mean length of hospital stay was significantly longer in the PMA infarction group (10.3 ± 9.1 days) than in the normal group (6.5 ± 6.4 days; p < 0.0001). The distribution of Glasgow Outcome Scale at discharge was significantly different between the two groups (p ≤ 0.0001) but was not so at 6 months after discharge (p = 0.0568). Multivariate logistic regression analysis identified aneurysm size (odds ratio [OR], 1.194; 95% confidence interval [CI], 1.08-1.32; p = 0.0005) and medial direction of aneurysm (OR, 4.615; 95% CI, 1.224-17.406; p = 0.0239) as independent risk factors of post-clipping PMA infarction. Surgeons must beware of PMA infarction after clipping of large aneurysms that are medial in direction. Intraoperative verification of the patency of the PCoA and the PMA from various angles using various intraoperative methods can reduce morbidity due to PMA infarction.
Subject(s)
Aneurysm, Ruptured , Intracranial Aneurysm , Aneurysm, Ruptured/surgery , Arteries , Humans , Infarction/etiology , Infarction/surgery , Intracranial Aneurysm/etiology , Intracranial Aneurysm/surgery , Microsurgery/adverse effects , Microsurgery/methods , Neurosurgical Procedures/methods , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
[Figure: see text].
Subject(s)
Acetylcysteine/pharmacology , Cerebral Hemorrhage/drug therapy , Free Radical Scavengers/therapeutic use , Selenium/pharmacology , Adult , Cerebral Hemorrhage/pathology , Female , Humans , Male , Middle Aged , Oxidative Stress/drug effects , Reactive Oxygen Species/antagonists & inhibitors , Treatment OutcomeABSTRACT
BACKGROUND AND PURPOSE: Cerebrovascular diseases are a leading cause of mortality after liver transplantation (LT). The prevalence of potentially hemorrhagic cerebrovascular diseases (HCVDs) that could cause a hemorrhagic stroke in patients with severe liver diseases has not been reported. We aimed to analyze the underlying prevalence of HCVDs that could lead to hemorrhagic strokes in LT recipients compared with that in previously healthy controls. METHODS: A retrospective study with 1,920 consecutive LT recipients and 24,681 adults who underwent a health checkup during the same period was conducted (January 2011-December 2016). The prevalence of cerebral aneurysms (CA), cerebral arteriovenous malformation (AVM), and cavernous malformation (CM) was evaluated using brain imaging, including computed tomography angiography, magnetic resonance imaging, magnetic resonance angiography, and digital subtraction angiography. RESULTS: The prevalence of CA and CM were 3.1% and 0.5%, respectively, in the LT group and 3.8% and 0.4%, respectively, in the control group. According to the location of the cerebral artery, paraclinoid internal carotid artery aneurysms (odds ratio [OR] 0.440; P = 0.009) had a lower prevalence in LT recipients than in healthy controls. Anterior communicating artery (OR 3.080; P = 0.002) and superior cerebellar artery (OR 8.767; P = 0.017) aneurysms had a higher prevalence in the LT group than in the control. The prevalence of AVM was significantly higher in LT recipients (0.26%) than in healthy controls (0.06%). CONCLUSION: LT recipients showed a different distribution of CA prevalence according to the locations of the cerebral artery and had a higher overall prevalence of AVM than previously healthy controls.
Subject(s)
Cerebrovascular Disorders , Hemorrhagic Stroke , Intracranial Aneurysm , Intracranial Arteriovenous Malformations , Liver Transplantation , Adult , Angiography, Digital Subtraction , Cerebral Angiography , Humans , Intracranial Aneurysm/complications , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/epidemiology , Prevalence , Retrospective StudiesABSTRACT
Postoperative ischemic complication results in neurological sequelae and longer hospitalization after unruptured middle cerebral artery (MCA) aneurysm clipping surgery. We evaluated the radiological and patient-related factors associated with ischemic complications after unruptured MCA aneurysm clipping surgery. Patient demographics, radiological findings, and intraoperative factors were compared between patients with and without postoperative ischemic complications. The clinical courses and outcomes of postoperative ischemic complications were compared according to the types of ischemic complication. Forty-two out of 2227 patients (1.9%) developed postoperative ischemic complications after MCA aneurysm clipping. Multivariate analysis revealed that diabetes mellitus (DM) was a patient-related factor. Intraarterial (IA) calcification of the distal internal carotid artery (ICA), preoperative M1 stenosis, and M1 aneurysm were radiological factors that increased the risk of postoperative ischemic complications. DM was significantly associated with divisional branch territory infarction (P = 0.04). The time to first presentation of ischemic complication was significantly longer in divisional branch territory infarction than perforator territory infarction (67.8 ± 75.9 h vs. 22 ± 20.7, P = 0.023). Twelve out of 42 patients with ischemic complications (28.6%) had unfavorable outcome (mRS > 3). Perforator territory infarction was significantly associated with an unfavorable outcome (mRS > 3, P = 0.019). IA calcification of the distal ICA, M1 stenosis and aneurysms, and DM were significantly associated with postoperative ischemic complications after unruptured MCA aneurysm clipping. Patients with DM should be closely monitored postoperatively to detect delayed occurrence of divisional branch infarction. Trial registration number: 2019-1002, Date of registration: January 1, 2005, "retrospectively registered".
Subject(s)
Cerebral Revascularization , Intracranial Aneurysm , Humans , Intracranial Aneurysm/complications , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Middle Cerebral Artery/diagnostic imaging , Middle Cerebral Artery/surgery , Neurosurgical Procedures , Postoperative Complications/epidemiology , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: Cerebral revascularization using the superficial temporal artery diverts some of the blood supply from the scalp to the brain. This may compromise the blood supply to the scalp and could result in more wound complications. OBJECTIVE: This retrospective chart review aimed to identify the incidence of, and independent risk factors for, wound complications after cerebral revascularization using the superficial temporal artery. METHODS: Patients who underwent cerebral revascularization using the superficial temporal artery between January 2003 and February 2017 were studied. Minor wound complications included superficial skin necrosis, and mild wound dehiscence, while major wound complications included full-thickness skin necrosis, deep infection, and osteomyelitis that required additional surgical treatment. RESULTS: A total of 482 cerebral revascularization procedures using the superficial temporal artery were included. Wound complications developed in 32 cases (6.6% of the total), including 7 classified as major in severity (1.5% of the total). The multivariate analysis revealed diabetes mellitus (odds ratio 4.058, p = 0.001), low body mass index (odds ratio 1.21, p = 0.009), and thin scalp (odds ratio 1.82, p < 0.001) as the main risk factors for wound complications. Every 1-mm increase in scalp thickness was associated with a protective effect on wound complications (odds ratio 0.549). CONCLUSION: Cerebral revascularization using the superficial temporal artery was associated with a relatively high incidence of wound complications. Diabetes mellitus, low body mass index, and thin scalp were found to be independent risk factors for wound complications. The thickness of the scalp could be a useful predictor of wound complications.
Subject(s)
Cerebral Revascularization/adverse effects , Postoperative Complications/epidemiology , Scalp/anatomy & histology , Adult , Cerebral Revascularization/methods , Female , Humans , Male , Middle Aged , Risk Factors , Scalp/surgery , Temporal Arteries/surgeryABSTRACT
BACKGROUND: Decompressive hemicraniectomy reduces secondary brain injury related to brain edema and increased intracranial pressure (ICP) in patients with malignant middle cerebral artery infarction (MMI). However, a substantial proportion of patients still die despite hemicraniectomy due to refractory brain swelling. OBJECTIVE: We aim to investigate whether ICP measured immediately after hemicraniectomy may indicate decompression effects and predict survival in patients with MMI. METHODS: We included 25 patients with MMI who underwent ICP monitoring and brain computed tomography within the first hour of hemicraniectomy. Midline shifts were measured as radiological surrogates of decompression. The Glasgow Coma Scale and pupillary enlargements during the first day after hemicraniectomy were assessed as clinical surrogates of decompression. Long-term survival status at 6 months was used as the final outcome. We analyzed the relationships between early ICP and findings of midline shift, Glasgow Coma Scale, pupillary enlargement, and survival. RESULTS: Initial ICP was correlated with mean ICP ( P < .001) and maximal ICP ( P < .001) during the first postoperative day. Intracranial pressure was associated with midline shifts ( P = .009), lower Glasgow Coma Scale scores ( P = .025), and the pupillary enlargement ( P = .015). Sixteen (64.0%) patients survived at 6 months. In a Cox proportional hazard model, elevated ICP was associated with mortality at 6 months (hazard ratio: 1.13; 95% confidence interval: 1.03-1.24; P = .008). CONCLUSION: Increase in ICP soon after hemicraniectomy was associated with midline shift, poor neurological status, and mortality in patients with MMI. Measurements of ICP soon after hemicraniectomy may permit earlier interventions as well as more refined clinical assessments.
Subject(s)
Brain Edema/mortality , Brain Neoplasms/mortality , Decompressive Craniectomy/mortality , Infarction, Middle Cerebral Artery/mortality , Intracranial Hypertension/mortality , Intracranial Pressure/physiology , Postoperative Complications/mortality , Aged , Brain Edema/diagnostic imaging , Brain Edema/etiology , Brain Neoplasms/physiopathology , Brain Neoplasms/surgery , Decompressive Craniectomy/methods , Female , Glasgow Coma Scale , Humans , Infarction, Middle Cerebral Artery/physiopathology , Infarction, Middle Cerebral Artery/surgery , Intracranial Hypertension/diagnostic imaging , Intracranial Hypertension/etiology , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Predictive Value of Tests , Proportional Hazards Models , Survival Rate , Tomography, X-Ray ComputedABSTRACT
Background: Nasal pretreatment with the neuropeptide oxytocin has been reported to prevent stress-induced impairments in hippocampal synaptic plasticity and spatial memory in rats. However, no study has asked if oxytocin application following a stress experience is effective in rescuing stress-induced impairments. Methods: Synaptic plasticity was measured in hippocampal Schaffer collateral-CA1 synapses of rats subjected to uncontrollable stress; their cognitive function was examined using an object recognition task. Results: Impaired induction of long-lasting, long-term potentiation by uncontrollable stress was rescued, as demonstrated both in rats and hippocampal slices. Intranasal oxytocin after experiencing uncontrollable stress blocked cognitive impairments in stressed rats and in stressed hippocampal slices treated with a perfused bath solution containing oxytocin. Conclusions: These results indicated that posttreatment with oxytocin after experiencing a stressful event can keep synaptic plasticity and cognition function intact, indicating the therapeutic potential of oxytocin for stress-related disorders, including posttraumatic stress disorder.
Subject(s)
Hippocampus/drug effects , Long-Term Potentiation/drug effects , Memory Disorders/drug therapy , Nootropic Agents/pharmacology , Oxytocin/pharmacology , Stress, Psychological/drug therapy , Administration, Intranasal , Animals , Disease Models, Animal , Hippocampus/physiopathology , Long-Term Potentiation/physiology , Male , Memory Disorders/etiology , Memory Disorders/physiopathology , Rats, Sprague-Dawley , Recognition, Psychology/drug effects , Recognition, Psychology/physiology , Stress, Psychological/physiopathology , Tissue Culture TechniquesABSTRACT
BACKGROUND: Fructus mume (F. mume) has been used as a traditional treatment for ulcer, cough, and digestive problems for many years in Asian countries. Previous studies have demonstrated that F. mume extracts alleviate cognitive deficits in rats with chronic cerebral hypoperfusion and in mice with scopolamine treatments. The present experiment was conducted to examine the effects of F. mume on cognitive impairments in 5XFAD transgenic mice with five familial Alzheimer's disease (AD) mutations. METHODS: F. mume was administered daily to 5XFAD mice at 12 weeks of age and continued for 90 days. Cognitive function was evaluated using a spatial memory version of the Morris water maze task, the object/location novelty recognition test, and contextual fear conditioning at 24 weeks of age. To elucidate the possible mechanisms underlying the memory improving effects of F. mume in 5XFAD mice, we examined alterations in hippocampal cholinergic function. RESULTS: Vehicle-treated 5XFAD mice exhibited hippocampus-dependent memory impairments compared with non-transgenic littermates, which was reversed in F. mume-treated 5XFAD mice. In addition, reduced hippocampal choline acetyltransferase (ChAT) levels in 5XFAD mice were reversed by F. mume treatment, indicating that F. mume enhances the effects of cholinergic neuronal function. CONCLUSIONS: F. mume may have therapeutic effects on cognitive impairments in AD.
Subject(s)
Cognition Disorders/drug therapy , Plants, Medicinal , Prunus , Alzheimer Disease , Animals , Choline O-Acetyltransferase/metabolism , Female , Fruit/chemistry , Hippocampus/enzymology , Humans , Male , Maze Learning/drug effects , Mice, TransgenicABSTRACT
BACKGROUND: One of the major causes for performing unplanned re-exploration of a craniotomy after microsurgery for unruptured intracranial aneurysms (UIAs) is compromised distal blood flow after clipping. Therefore, it is important to identify the causes of compromised distal blood flow after clipping and the factors that influence the prognosis for re-exploration in order to decrease ischemic complications related to clipping UIAs. METHOD: Between January 2007 and December 2013, 1954 patients underwent microsurgery for UIAs. In this cohort, 20 patients (1.0%) required unplanned re-exploration of the craniotomy for several reasons, and 11 patients (0.6%) underwent unplanned re-exploration with clip repositioning or changing of the previous clip because of compromised distal blood flow after clipping. Patient characteristics, aneurysm properties, intraoperative findings, annual incidence and prognosis were analyzed in these 11 patients. RESULTS: The annual incidence of re-exploration has gradually decreased since the introduction of several intraoperative monitoring techniques. In total, 3.0% of UIAs in the M1 trunk, 0.8% of UIAs at the origin of the anterior choroidal artery (AchA) and 0.5% of UIAs at the bifurcation of the middle cerebral artery (MCA) required re-exploration. Here, all 11 UIAs had broad necks, and atherosclerosis was identified around 10 UIAs. Six patients with compromised MCA flow demonstrated relatively better outcomes following re-exploration than five patients with a compromised lenticulostriate artery (LSA) or AchA flow. Four patients with delayed ischemic symptoms demonstrated relatively better outcomes than the seven patients who developed ischemic symptoms immediately postoperatively. CONCLUSION: Clinicians need to be more careful not to compromise distal blood flow when clipping UIAs at the MCA and AchA origin. Various intraoperative monitoring techniques can help reduce the incidence of compromised distal blood flow after clipping.
Subject(s)
Brain Ischemia/surgery , Cerebral Arteries/surgery , Cerebrovascular Circulation/physiology , Craniotomy/adverse effects , Intracranial Aneurysm/surgery , Microsurgery/adverse effects , Aged , Brain Ischemia/etiology , Brain Ischemia/physiopathology , Cerebral Arteries/physiopathology , Female , Humans , Intracranial Aneurysm/physiopathology , Male , Middle Aged , Monitoring, Intraoperative , Reoperation , Surgical InstrumentsABSTRACT
BACKGROUND: Dissecting aneurysms of the posterior cerebral artery (PCA) are rare and difficult to treat because of their deep and unfamiliar locations and unusual shapes. Although several treatment modalities have been proposed, none have generated satisfying results. Our experiences with PCA-dissecting aneurysms are reviewed and the treatment strategies discussed. METHODS: All consecutive patients with PCA-dissecting aneurysm who were treated in a tertiary referral hospital between January 1998 and March 2014 were identified by retrospective review. Their clinical characteristics, radiological findings, treatment modalities and outcomes were documented. RESULTS: Of the 21 patients with 21 PCA-dissecting aneurysms, 9 had subarachnoid hemorrhage and 3 had acute infarction of the thalamus at presentation. The aneurysms involved P1 (n = 4), the P1-2 junction (n = 3), mid-P2 (n = 6), P2A (n = 3), P2P (n = 1) and the P2-3 junction (n = 4). The aneurysm shapes were as follows: fusiform (n = 12), partially thrombosed (n = 8) and blood blister-like aneurysms (n = 1). The mean size was 16.6 ± 9.7 mm. Parent artery occlusion (PAO) without bypass (n = 15), PAO with bypass (n = 2), stent-assisted endosaccular coiling (n = 3) and stent placement only (n = 1) were performed. All three patients who underwent stent-assisted endosaccular coiling and the single patient who underwent PAO without bypass developed aneurysm recurrence. Six of the ten patients who received a PAO without a balloon test occlusion (BTO) experienced PCA territory infarction, whereas only one of the five patients who received a PAO after passing the BTO experienced an infarction. CONCLUSIONS: PAO for PCA-dissecting aneurysm was effective in preventing recurrence. In addition, BTO before PAO was helpful in identifying candidates who truly needed surgical revascularization.
Subject(s)
Aortic Dissection/surgery , Cerebral Revascularization/adverse effects , Embolization, Therapeutic/adverse effects , Endovascular Procedures/adverse effects , Intracranial Aneurysm/surgery , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Unplanned re-exploration of the craniotomy after surgical treatment of unruptured intracranial aneurysms (UIAs) is sometimes required, but the underlying causes and rates of these procedures are seldom reported. This study retrospectively analyzed the causes of such re-explorations to identify methods for decreasing their necessity. METHOD: From January 2000 to December 2011, 1,720 patients with a total of 1,938 UIAs underwent surgical treatment at our institution. From this cohort, 26 patients (1.5 %) with 38 UIAs required re-exploration. Clinical data, aneurysm characteristics, treatment methods, and the incidence and causes of re-exploration of the craniotomy were analyzed for these 26 patients. RESULTS: Several causes of re-exploration were identified: compromised distal blood flow (eight patients, 0.47 %), hemorrhagic venous infarction (four patients, 0.23 %), brain retraction injury (three patients, 0.17 %), newly identified aneurysms (three patients, 0.17 %), bleeding from an incompletely clipped aneurysm (two patients, 0.12 %), epidural hematoma (two patients, 0.12 %), failed aneurysm clipping (two patients, 0.12 %) and other causes (two patients, 0.12 %). Annual re-exploration incidence rates ranged from 0 to 3.1 %. Annual incidence rates gradually decreased following the introduction of several intraoperative monitoring systems. CONCLUSIONS: Precise surgical planning and careful operative techniques can reduce the incidence of unplanned re-exploration of the craniotomy. The introduction of various intraoperative monitoring systems can also contribute to a reduction in this incidence.
Subject(s)
Craniotomy/statistics & numerical data , Intracranial Aneurysm/surgery , Postoperative Complications , Reoperation/statistics & numerical data , Vascular Surgical Procedures , Aged , Female , Humans , Incidence , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies , Treatment Outcome , Vascular Surgical Procedures/adverse effects , Vascular Surgical Procedures/standards , Vascular Surgical Procedures/statistics & numerical dataABSTRACT
OBJECTIVE: The purpose of this study was to analyze the characteristics of partially thrombosed intracranial aneurysms (PTIAs) in terms of location, shape, size, and symptoms, and to assess outcome according to the type of treatment. METHODS: We reviewed the radiological and clinical findings of 35 cases of PTIAs followed in our institution between 2006 and 2011. We divided all treatment modalities into two groups. Patients in group A (n = 15) were treated by blood flow blockage from the lesion of the pathogenic segment of the parent where the PTIAs originated, and patients in group B (n = 20) were only treated with obliteration of the remnant perfused aneurysmal sac. Radiological and clinical outcomes of treatment were compared between the two groups. RESULTS: Group A showed complete occlusion in 15 cases (100 %) compared to six cases (30.0 %) in group B (p < 0.001). No cases required retreatment in group A, while six cases (30.0 %) underwent retreatment in group B (p = 0.027). In terms of clinical outcome, 12 cases (80.0 %) showed symptomatic improvement in group A compared to eight cases (40.0 %) in group B (p = 0.037). Nine cases (60.0 %) showed improvement in postoperative GOS at six months compared to initial preoperative GOS in group A versus four (20.0 %) in group B (p = 0.032). CONCLUSION: PTIAs should be treated by preventing blood flow from the lesion of the pathogenic segment of the parent artery where PTIAs originate. This treatment approach is associated with better clinical and radiological outcomes.
Subject(s)
Intracranial Aneurysm/therapy , Adolescent , Adult , Aged , Cohort Studies , Combined Modality Therapy , Disability Evaluation , Embolization, Therapeutic , Female , Humans , Intracranial Thrombosis/therapy , Male , Middle Aged , Retreatment , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
Objective: We evaluated the role of subgaleal closed suction drains in postoperative epidural hematoma (EDH) and wound complications following pterional craniotomy for cerebral aneurysm. Methods: We reviewed 5,280 pterional craniotomies performed on 5,139 patients between January 2006 and December 2020. A drain was placed subgalealy and tip of drain was positioned between the bone flap and the deep temporalis. 1,637 cases (31%) had a subgaleal suction drain. We analyzed demographic and clinical variables related to EDH requiring evacuation and wound complications in patients with and without drains. Univariate and multivariate logistic regression analyses were performed to determine the associated risk factors. Results: Fourteen cases (0.27%) of EDH requiring evacuation and 30 cases (0.57%) of wound complications were identified. Univariate analysis found that drain insertion, subarachnoid hemorrhage (SAH), and operation time were associated with EDH, while drain insertion, SAH, male gender, older age, and longer operation time were associated with wound complications. Multivariate analysis found no significant association between drain use and EDH (OR=1.62, p=0.402) or wound complications (OR=1.45, p=0.342). Conclusions: Routine use of subgaleal closed suction drains may not be necessary after pterional craniotomy, as drain insertion was not associated with a reduced risk of EDH requiring evacuation or wound complications.