The Transient Receptor Potential Melastatin 7 (TRPM7) Inhibitors Suppress Seizure-Induced Neuron Death by Inhibiting Zinc Neurotoxicity.

Transient receptor potential melastatin 7 (TRPM7) is an ion channel that mediates monovalent cations out of cells, as well as the entry of divalent cations, such as zinc, magnesium, and calcium, into the cell. It has been reported that inhibitors of TRPM7 are neuroprotective in various neurological diseases. Previous studies in our lab suggested that seizure-induced neuronal death may be caused by the excessive release of vesicular zinc and the subsequent accumulation of zinc in the neurons. However, no studies have evaluated the effects of carvacrol and 2-aminoethoxydiphenyl borate (2-APB), both inhibitors of TRPM7, on the accumulation of intracellular zinc in dying neurons following seizure. Here, we investigated the therapeutic efficacy of carvacrol and 2-APB against pilocarpine-induced seizure. Carvacrol (50 mg/kg) was injected once per day for 3 or 7 days after seizure. 2-APB (2 mg/kg) was also injected once per day for 3 days after seizure. We found that inhibitors of TRPM7 reduced seizure-induced TRPM7 overexpression, intracellular zinc accumulation, and reactive oxygen species production. Moreover, there was a suppression of oxidative stress, glial activation, and the blood-brain barrier breakdown. In addition, inhibitors of TRPM7 remarkably decreased apoptotic neuron death following seizure. Taken together, the present study demonstrates that TRPM7-mediated zinc translocation is involved in neuron death after seizure. The present study suggests that inhibitors of TRPM7 may have high therapeutic potential to reduce seizure-induced neuron death.

Protective Effects of Protocatechuic Acid on Seizure-Induced Neuronal Death.

Protocatechuic acid (PCA) is a type of phenolic acid found in green tea and has been shown to have potent antioxidant and anti-inflammatory properties. However, the effect of PCA on pilocarpine seizure-induced neuronal death in the hippocampus has not been evaluated. In the present study, we investigated the potential therapeutic effects of PCA on seizure-induced brain injury. Epileptic seizure was induced by intraperitoneal (i.p.) injection of pilocarpine (25 mg/kg) in adult male rats, and PCA (30 mg/kg) was injected into the intraperitoneal space for three consecutive days after the seizure. Neuronal injury and oxidative stress were evaluated three days after a seizure. To confirm whether PCA increases neuronal survival and reduced oxidative injury in the hippocampus, we performed Fluoro-Jade-B (FJB) staining to detect neuronal death and 4-hydroxynonenal (4HNE) staining to detect oxidative stress after the seizure. In the present study, we found that, compared to the seizure vehicle-treated group, PCA administration reduced neuronal death and oxidative stress in the hippocampus. To verify whether a decrease of neuronal death by PCA treatment was due to reduced glutathione (GSH) concentration, we measured glutathione with N-ethylmaleimide (GS-NEM) levels in hippocampal neurons. A seizure-induced reduction in the hippocampal neuronal GSH concentration was preserved by PCA treatment. We also examined whether microglia activation was affected by the PCA treatment after a seizure, using CD11b staining. Here, we found that seizure-induced microglia activation was significantly reduced by the PCA treatment. Therefore, the present study demonstrates that PCA deserves further investigation as a therapeutic agent for reducing hippocampal neuronal death after epileptic seizures.

Effects of Protocatechuic Acid (PCA) on Global Cerebral Ischemia-Induced Hippocampal Neuronal Death.

Global cerebral ischemia (GCI) is one of the main causes of hippocampal neuronal death. Ischemic damage can be rescued by early blood reperfusion. However, under some circumstances reperfusion itself can trigger a cell death process that is initiated by the reintroduction of blood, followed by the production of superoxide, a blood⁻brain barrier (BBB) disruption and microglial activation. Protocatechuic acid (PCA) is a major metabolite of the antioxidant polyphenols, which have been discovered in green tea. PCA has been shown to have antioxidant effects on healthy cells and anti-proliferative effects on tumor cells. To test whether PCA can prevent ischemia-induced hippocampal neuronal death, rats were injected with PCA (30 mg/kg/day) per oral (p.o) for one week after global ischemia. To evaluate degenerating neurons, oxidative stress, microglial activation and BBB disruption, we performed Fluoro-Jade B (FJB), 4-hydroxynonenal (4HNE), CD11b, GFAP and IgG staining. In the present study, we found that PCA significantly decreased degenerating neuronal cell death, oxidative stress, microglial activation, astrocyte activation and BBB disruption compared with the vehicle-treated group after ischemia. In addition, an ischemia-induced reduction in glutathione (GSH) concentration in hippocampal neurons was recovered by PCA administration. Therefore, the administration of PCA may be further investigated as a promising tool for decreasing hippocampal neuronal death after global cerebral ischemia.

Inhibition of NADPH Oxidase Activation by Apocynin Rescues Seizure-Induced Reduction of Adult Hippocampal Neurogenesis.

Apocynin, also known as acetovanillone, is a natural organic compound structurally related to vanillin. Apocynin is known to be an inhibitor of NADPH (Nicotinamide adenine dinucleotide phosphate) oxidase activity and is highly effective in suppressing the production of superoxide. The neuroprotective effects of apocynin have been investigated in numerous brain injury settings, such as stroke, traumatic brain injury (TBI), and epilepsy. Our lab has demonstrated that TBI or seizure-induced oxidative injury and neuronal death were reduced by apocynin treatment. Several studies have also demonstrated that neuroblast production is transiently increased in the hippocampus after seizures. Here, we provide evidence confirming the hypothesis that long-term treatment with apocynin may enhance newly generated hippocampal neuronal survival by reduction of superoxide production after seizures. A seizure was induced by pilocarpine [(25 mg/kg intraperitoneal (i.p.)] injection. Apocynin was continuously injected for 4 weeks after seizures (once per day) into the intraperitoneal space. We evaluated neuronal nuclear antigen (NeuN), bromodeoxyuridine (BrdU), and doublecortin (DCX) immunostaining to determine whether treatment with apocynin increased neuronal survival and neurogenesis in the hippocampus after seizures. The present study indicates that long-term treatment of apocynin increased the number of NeuN⁺ and DCX⁺ cells in the hippocampus after seizures. Therefore, this study suggests that apocynin treatment increased neuronal survival and neuroblast production by reduction of hippocampal oxidative injury after seizures.

Are the anomalous vertebral arteries more hypoplastic?: retrospective linear mixed model approach.

BACKGROUND: Small or hypoplastic vertebral artery (VA) is one of the risk factor for posterior circulation stroke. We assess whether various types of VA anomaly contribute to its diameter. METHODS: We screened 238 patients who underwent neck CT and MR angiography within 1 month. A V1 anomaly was defined as the abnormal origin of the VA on a three-dimensional MR angiography and a V2 anomaly was defined as the VA not passing through the 6th cervical transverse foramen (TF) on an axial CT image. A linear mixed model was used to evaluate the determinants of VA size. RESULTS: Among participants, 24 (10.1%) subjects exhibited an anomalous VA and, of the 476 VAs examined, 11 (2.3%) had an aortic origin and 27 (5.7%) had an abnormal entrance into the C6 TF. Presence of the V1 anomaly was positively associated with the V2 anomaly (P for chi-square < 0.001) and a linear mixed model revealed that being male (0.2 mm larger, P = 0.015), having a right VA anomaly (0.3 mm smaller, P < 0.001), having a V1 anomaly (0.9 mm smaller, P < 0.001), and having a V2 anomaly (0.7 mm smaller, P < 0.001) were significant predictor of VA diameter. CONCLUSION: The diameters of VAs with an anomalous aortic origin or an abnormal entrance of the TF were significantly smaller than those of normal VAs. These findings suggest that anomalies of the VA detected in 3-dimensional CTA or MRA may be clues for vertebral artery hypoplasia.

Diverse Effects of an Acetylcholinesterase Inhibitor, Donepezil, on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure.

Epileptic seizures are short episodes of abnormal brain electrical activity. Many survivors of severe epilepsy display delayed neuronal death and permanent cognitive impairment. Donepezil is an acetylcholinesterase inhibitor and is an effective treatment agent for Alzheimer's disease. However, the role of donepezil in seizure-induced hippocampal injury remains untested. Temporal lobe epilepsy (TLE) was induced by intraperitoneal injection of pilocarpine (25 mg/kg). Donepezil (2.5 mg/kg/day) was administered by gavage in three different settings: (1) pretreatment for three days before the seizure; (2) for one week immediately after the seizure; and (3) for three weeks from three weeks after the seizure. We found that donepezil showed mixed effects on seizure-induced brain injury, which were dependent on the treatment schedule. Pretreatment with donepezil aggravated neuronal death, oxidative injury, and microglia activation. Early treatment with donepezil for one week showed neither adverse nor beneficial effects; however, a treatment duration of three weeks starting three weeks after the seizure showed a significant reduction in neuronal death, oxidative injury, and microglia activation. In conclusion, donepezil has therapeutic effects when injected for three weeks after seizure activity subsides. Therefore, the present study suggests that the therapeutic use of donepezil for epilepsy patients requires a well-conceived strategy for administration.

Differences in cognitive function between patients with viral and alcoholic compensated liver cirrhosis.

As alcohol induces change in frontal cortex primarily involved in cognition, cognitive function may be different between viral and alcoholic liver cirrhosis (LC). This study aimed to determine the differences of cognitive function between viral and alcoholic compensated LC. From October 2011 to March 2013, 80 patients (viral: 37; alcohol: 43) with compensated LC were prospectively enrolled. Neuropsychological functions including attention, language, visuospatial, verbal memory, visual memory, and frontal/executive function were evaluated between two groups and compared with age-matched normal group (n = 1000). Cumulative incidence rate of overt hepatic encephalopathy (HE) was calculated. In the comparison with normal group, both two groups showed decreased memory function, frontal/executive function, and Korea-Mini Mental Status Examination. In the analysis of two groups, memory function by Verbal Learning Test (recognition: 20.1 ± 3.6 and 17.8 ± 4.8, p = 0.022), visuospatial function by Ray-Complex Figure Copy Test (recognition: 19.0 ± 2.6 and 17.3 ± 4.0, p = 0.043), frontal/executive function by Controlled Oral Ward Association (semantic: 17.1 ± 6.9 and 12.7 ± 6.9, p = 0.004), and the Korea-Mini Mental Status Examination (27.5 ± 1.9 and 26.2 ± 3.1, p = 0.03) showed low scores in alcoholic compensated LC patients. The 1-, 2-, and 3-year cumulative incidence rates of overt HE were 23%, 26%, and 26% and 33%, 43%, and 49% in the viral and alcoholic compensated LC group, respectively (p = 0.033). Impaired memory and frontal lobe executive functions and early development of overt HE were more common in patients with alcoholic LC. For patients with alcoholic LC, more integrated tests for early detection of minimal HE and intensive treatment should be considered to prevent overt HE.

Differences in central facilitation between episodic and chronic migraineurs in nociceptive-specific trigeminal pathways.

BACKGROUND: The trigeminal nociceptive system plays a pivotal role in the pathophysiology of migraines. The present study investigated whether there are differences between patients with episodic migraine (EM) and patients with chronic migraine (CM) in trigeminal pain processing at the brainstem and cortical levels using the nociceptive blink reflex (nBR) and pain-related evoked potentials (PREP). METHODS: This study assessed 68 female migraineurs (38 EM patients and 30 CM patients) and 40 age-matched controls using simultaneous recordings of nBR and PREP during the interictal period. RESULTS: In terms of the nBR, EM patients displayed significantly decreased latencies and larger amplitudes and area-under-the-curve (AUC) values for the R2 component, whereas CM patients showed significantly prolonged latencies and smaller amplitudes and AUC values for the R2 component (p < 0.05). In terms of PREP, both the EM and CM patients had decreased latencies (N1, P1), with larger amplitude compared with the controls (p < 0.05), which indicates facilitation at the cortical level. Additionally, the amplitude and AUC values of the R2 component exhibited a negative correlation, whereas the latency of the R2 component for the nBR showed a positive correlation, with the frequency of headaches in migraineurs (p < 0.01). CONCLUSIONS: In the present study, the facilitation in the trigeminal nociceptive pathway of the EM group suggests the occurrence of migraine-specific hyperexcitability. Additionally, the suppression of R2 at the brainstem level in the CM group may relate to impaired or dysfunctional descending pain modulation. These findings suggest that there are adaptive or maladaptive responses due to the chronification of migraine attacks.

Subclinical vestibular dysfunction in migraine patients: a preliminary study of ocular and rectified cervical vestibular evoked myogenic potentials.

BACKGROUND: Many studies have identified various vestibular symptoms and laboratory abnormalities in migraineurs. Although the vestibular tests may be abnormal, the changes may exist without vestibular symptoms. To date, vestibular-evoked myogenic potential (VEMP) has been the easiest and simplest test for measuring vestibular function in clinical practice. Cervical VEMP (cVEMP) represents a vestibulo-collic reflex, whereas ocular VEMP (oVEMP) reflects a vestibulo-ocular pathway. Therefore, we determined whether ocular and rectified cervical VEMPs differed in patients with migraine or tension type headache (TTH) and compared the results to controls with no accompanying vestibular symptoms. METHODS: The present study included 38 females with migraine without aura, 30 with episodic TTH, and 50 healthy controls without vestibular symptoms. oVEMP and cVEMP using a blood pressure manometer were recorded during a headache-free period. From the VEMP graphs, latency and amplitude parameters were analyzed, especially following EMG rectification in cVEMP. RESULTS: With respect to oVEMP, the migraine group exhibited significantly longer mean latencies of bilateral n1 and left p1 than the other groups (p < 0.05). Amplitudes of n1-p1 were lower than in other groups, but the difference did not reach statistical significance. In regards to cVEMP, p13 and n23 latencies and amplitudes after rectification did not differ significantly among groups. CONCLUSIONS: An abnormal interictal oVEMP profile was associated with subclinical vestibular dysfunction in migraineurs, suggesting pathology within the vestibulo-ocular reflex. oVEMP is a more reliable measure than cVEMP to evaluate vestibular function in migraineurs, although results from the two tests in patients with migraine are complementary.

Fulminant cerebral infarction of anterior and posterior cerebral circulation after ascending type of facial necrotizing fasciitis.

Necrotizing fasciitis is a soft tissue infection that is characterized by extensive necrosis of the subcutaneous fat, neurovascular structures, and fascia. Cerebral infarction after facial necrotizing fasciitis has been rarely reported. A 61-year-old woman with diabetes was admitted with painful swelling of her right cheek. One day later, she was stuporous and quadriplegic. A computed tomographic scan of her face revealed right facial infection in the periorbital soft tissue, parotid, buccal muscle, and maxillary sinusitis. A computed tomographic scan of the brain revealed cerebral infarction in the right hemisphere, left frontal area, and both cerebellum. Four days later, she died from cerebral edema and septic shock. Involvement of the cerebral vasculature, such as the carotid or vertebral artery by necrotizing fasciitis, can cause cerebral infarction. Facial necrotizing fasciitis should be treated early with surgical treatment and the appropriate antibiotic therapy.

Machine Learning Model for Mild Cognitive Impairment Stage Based on Gait and MRI Images.

In patients with mild cognitive impairment (MCI), a lower level of cognitive function is associated with a higher likelihood of progression to dementia. In addition, gait disturbances and structural changes on brain MRI scans reflect cognitive levels. Therefore, we aimed to classify MCI based on cognitive level using gait parameters and brain MRI data. Eighty patients diagnosed with MCI from three dementia centres in Gangwon-do, Korea, were recruited for this study. We defined MCI as a Clinical Dementia Rating global score of ≥0.5, with a memory domain score of ≥0.5. Patients were classified as early-stage or late-stage MCI based on their mini-mental status examination (MMSE) z-scores. We trained a machine learning model using gait and MRI data parameters. The convolutional neural network (CNN) resulted in the best classifier performance in separating late-stage MCI from early-stage MCI; its performance was maximised when feature patterns that included multimodal features (GAIT + white matter dataset) were used. The single support time was the strongest predictor. Machine learning that incorporated gait and white matter parameters achieved the highest accuracy in distinguishing between late-stage MCI and early-stage MCI.

A phosphodiesterase 4 (PDE4) inhibitor, amlexanox, reduces neuroinflammation and neuronal death after pilocarpine-induced seizure.

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP). In pathological states, including epilepsy, increased PDE4 activity contributes to a decrease in cAMP levels, which may exacerbate neuroinflammatory responses. We hypothesized that amlexanox, an anti-inflammatory drug and non-selective PDE4 inhibitor, could offer neuroprotection by addressing lysosomal dysfunction and mitigating neuroinflammation, ultimately preventing neuronal death in epileptic conditions. Our research utilized a pilocarpine-induced epilepsy animal model to investigate amlexanox's potential benefits. Administered intraperitoneally at a dose of 100 â€‹mg/kg daily following the onset of a seizure, we monitored its effects on lysosomal function, inflammation, neuronal death, and cognitive performance in the brain. Tissue samples from various brain regions were collected at predetermined intervals for a comprehensive analysis. The study's results were significant. Amlexanox effectively improved lysosomal function, which we attribute to the modulation of zinc's influx into the lysosomes, subsequently enhancing autophagic processes and decreasing the release of inflammatory factors. Notably, this led to the attenuation of neuronal death in the hippocampal region. Additionally, cognitive function, assessed through the modified neurological severity score (mNSS) and the Barnes maze test, showed substantial improvements after treatment with amlexanox. These promising outcomes indicate that amlexanox has potential as a therapeutic agent in the treatment of epilepsy and related brain disorders. Its ability to combat lysosomal dysfunction and neuroinflammation positions it as a potential neuroprotective intervention. While these findings are encouraging, further research and clinical trials are essential to fully explore and validate the therapeutic efficacy of amlexanox in epilepsy management.

Effects of L-Type Voltage-Gated Calcium Channel (LTCC) Inhibition on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure.

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca2+) and other metal ions, such as zinc (Zn2+) and magnesium (Mg2+), into the cytosol. This Ca2+ influx at the presynaptic terminal triggers the release of Zn2+ and glutamate to the postsynaptic terminal. Zn2+ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn2+ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn2+ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn2+ accumulation, oxidative stress, and neuronal death. Our findings show that AML's LTCC inhibition decreased excessive Zn2+ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine's potential as a therapeutic agent in seizure management and mitigating seizures' detrimental effects.

Differences between episodic and chronic tension-type headaches in nociceptive-specific trigeminal pathways.

BACKGROUND: The trigeminal nociceptive system plays a pivotal role in the pathophysiology of tension-type headaches (TTH). OBJECTIVE: This study investigated and compared nociceptive-specific trigeminal pathways in patients with episodic and chronic TTH (ETTH and CTTH, respectively) using the nociceptive blink reflex (nBR) and nociceptive trigeminocervical reflex (nTCR). METHODS: We recorded nBR and nTCR in patients with ETTH and CTTH, and healthy controls using concentric electrodes and subsequently compared the threshold (i.e. sensory, pain) and parameters of reflex (i.e. the R2 component of the nBR and the late responses of the nTCR). RESULTS: Women with ETTH ( N = 40) and CTTH ( N = 32) and age-matched controls ( N = 40) were recruited. CTTH patients displayed significantly lower amplitude and area under the curve (AUC) values of the R2 component for the nBR compared with those displayed by ETTH patients and controls ( P < 0.05). Moreover, the amplitude and AUC of the R2 component was negatively correlated with the frequency of headaches, whereas the latency of the R2 component for the nBR was positively correlated with the frequency and duration of headaches in the TTH groups ( P < 0.05). However, no significant differences in the late response parameters (i.e. latency, duration, amplitude, or AUC) were noted between the groups in terms of the nTCR. CONCLUSIONS: R2 suppression associated with CTTH suggests decreased brainstem excitability. This may be the result of excessive descending inhibitory influences.

Relationship of Neural Correlates of Gait Characteristics and Cognitive Dysfunction in Patients with Mild Cognitive Impairment.

Background: Some patients with mild cognitive impairment (MCI) experience gait disturbances. However, there are few reports on the relationship between gait disturbance and cognitive function in patients with MCI. Therefore, we investigated the neural correlates of gait characteristics related to cognitive dysfunction. Methods: Eighty patients diagnosed with MCI from three dementia centers in Gangwon-do, Korea, were recruited for this study. We defined MCI as a Clinical Dementia Rating global score of 0.5 or higher, with a memory domain score of 0.5 or greater. The patients were classified as having either higher or lower MMSE and the groups were based on their Mini Mental Status Examination z-scores. Multiple logistic regression analysis was performed to examine the association between the gait characteristics and cognitive impairment. Analyses included variables such as age, sex, years of education, number of comorbidities, body mass index, and height. Results: Gait velocity, step count, step length, heel-to-heel base support, swing and stance phase duration, and support time were associated with cognitive function. A decrease in gray matter volume in the right pericalcarine area was associated with gait characteristics related to cognitive dysfunction. An increase in the curvature of gray matter in the right entorhinal, right lateral orbitofrontal, right cuneus, and right and left pars opercularis areas was also associated with gait characteristics related to cognitive dysfunction. Conclusion: Since gait impairment is an important factor in determining activities of daily living in patients with mild cognitive impairment, the evaluation of gait and cognitive functions in patients with mild cognitive impairment is important.

The roles of P2X7 receptor in regional-specific microglial responses in the rat brain following status epilepticus.

Recently, we have reported that astroglial activations in response to status epilepticus (SE) show regional-specific manners in the rat hippocampus. However, it is unknown that microglial responses to SE would show regional-specific patterns. Therefore, the present study was designed to elucidate the regional-specific microglial activation and relationship between P2X7 receptor functions and SE-induced microglial responses in the rat brain. Following SE, microglia appeared amoeboid or phagocytic in the dentate gyrus and the piriform cortex. In contrast, elongated microglia were observed in the CA1 hippocampal regions and the frontoparietal cortex. In the dentate gyrus, the CA1 hippocampal regions, and the frontoparietal cortex, these microglial activation accelerated by BzATP (a P2X7 receptor agonist)-infusion, but inhibited by OxATP (a P2X7 receptor antagonist). However, SE-induced microglial activation in the piriform cortex was not affected by BzATP or OxATP-infusion. Therefore, our findings indicate that SE-induced microglial activation may show regional-specific manners, and suggest that P2X7 receptor function differently modulates SE-induced microglial responses in distinct brain regions.

Acute cerebellar infarction associated with intravenous gammaglobulin treatment in idiopathic thrombocytopenic purpura.

Intravenous immunoglobulins (IVIGs) are used for a variety of immunologic and hematologic disorders. Hemorheologic alteration or the rapid increase of platelet counts by IVIG administration can cause thrombotic adverse events. We present a 58-year-old woman with a previous diagnosis of idiopathic thrombocytopenic purpura who developed cerebellar infarction immediately after IVIG treatment. We discuss a possible role of IVIG in cerebral ischemia and management strategies.

Clinical Factors Contributing to Cognitive Function in the Acute Stage after Treatment of Intracranial Aneurysms: A Cross-Sectional Study.

Background: The factors affecting cognitive function after treatment of subarachnoid haemorrhage (SAH) can be categorised into aneurysmal factors, procedural factors, and complications. The aim of this study was to investigate which of these factors has greater influence on the cognitive function. Methods: We retrospectively identified 14 patients with unruptured intracranial aneurysms (UIAs) and 34 patients with SAH with mild symptoms at disease onset (Hunt and Hess grade: >3). All patients underwent neuropsychological tests within 35 days of discharge from hospitalisation for treatment. The relationship between the clinical factors and each neuropsychological test score was evaluated using multiple linear regression analysis after controlling for age and years of education. Results: Patients with UIA showed greater cognitive impairment in visual memory and the frontal/executive domains. Hypertension was associated with cognitive impairment. Patients with SAH showed greater cognitive impairment in the visuospatial, verbal memory, and frontal/executive domains. The dome-to-neck ratio, aneurysms located in the posterior circulation, microsurgical clipping, procedure time, anaesthesia duration, and complications were associated with cognitive impairment. Conclusions: Underlying diseases, procedural factors, and complications contributed to cognitive impairment after treatment of intracranial aneurysms. Since the effect of each factor on each cognitive domain was slightly different, a more in-depth study of these effects is needed.

Effect of right hemispheric damage on structured spoken conversation.

Patients with right hemisphere damage (RHD) occasionally complain of difficulties in conversation. A conversation is a type of communication between the speaker and listener, and several elements are required for a conversation to take place. However, it is unclear which of those elements affect communication in patients with RHD. Therefore, we prospectively enrolled 11 patients with right hemispheric damage due to acute cerebral infarction, within 1 week of onset. To evaluate patients' conversational abilities, we used a structured conversation task, namely, the "Hallym Conversation and Pragmatics Protocol". The topics of conversation were "family", "leisure", and "other/friends". The conversation characteristics were classified according to three indices: the "conversational participation index", "topic manipulation index", and "conversational breakdown index". Patients with RHD were compared with 11 age-, sex-, and years of education-matched healthy adults. The most common site of damage in the patients with RHD was the periventricular white matter. There was no significant difference in performance between the two groups according to the conversation participation index and in the discontinuance rate assessed with the conversational breakdown index. However, patients with RHD showed a lower topic maintenance rate and higher topic initiation and topic switching rates, according to the topic manipulation index. Therefore, we explored the characteristics of impaired conversation abilities in patients with RHD by assessing their ability to converse and manage topics during structured conversations, and found difficulties with pragmatics and communication discourse in these patients.

Combined Treatment of Dichloroacetic Acid and Pyruvate Increased Neuronal Survival after Seizure.

During seizure activity, glucose and Adenosine triphosphate (ATP) levels are significantly decreased in the brain, which is a contributing factor to seizure-induced neuronal death. Dichloroacetic acid (DCA) has been shown to prevent cell death. DCA is also known to be involved in adenosine triphosphate (ATP) production by activating pyruvate dehydrogenase (PDH), a gatekeeper of glucose oxidation, as a pyruvate dehydrogenase kinase (PDK) inhibitor. To confirm these findings, in this study, rats were given a per oral (P.O.) injection of DCA (100 mg/kg) with pyruvate (50 mg/kg) once per day for 1 week starting 2 h after the onset of seizures induced by pilocarpine administration. Neuronal death and oxidative stress were assessed 1 week after seizure to determine if the combined treatment of pyruvate and DCA increased neuronal survival and reduced oxidative damage in the hippocampus. We found that the combined treatment of pyruvate and DCA showed protective effects against seizure-associated hippocampal neuronal cell death compared to the vehicle-treated group. Treatment with combined pyruvate and DCA after seizure may have a therapeutic effect by increasing the proportion of pyruvate converted to ATP. Thus, the current research demonstrates that the combined treatment of pyruvate and DCA may have therapeutic potential in seizure-induced neuronal death.