Effects of frailty on postoperative clinical outcomes of aneurysmal subarachnoid hemorrhage: results from the National Inpatient Sample database.

BACKGROUND: This study aimed to investigate the potential effect of preoperative frailty on postoperative clinical outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Data of patients aged 18 years and older who were diagnosed with subarachnoid hemorrhage or intracerebral hemorrhage, underwent aneurysm repair surgical intervention from 2005 to 2014. A retrospective database analysis was performed based on U.S. National Inpatient Sample (NIS) from 2005 to 2014. Frailty was determined using the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnoses indicator. Patients were stratified into frail and non-frail groups and the study endpoints were incidence of postoperative complications and related adverse clinical outcomes. RESULTS: Among 20,527 included aSAH patients, 2303 (11.2%) were frail and 18,224 (88.8%) were non-frail. Significant differences were found between frailty and non-frailty groups in the four clinical outcomes (all p < 0.05). Multivariate analysis showed that frailty was associated with significant higher risks of discharge to institutional care (aOR: 2.50, 95%CI: 2.10-2.97), tracheostomy or gastrostomy tube replacement (aOR: 4.41, 95%CI: 3.81-5.10) and postoperative complications (aOR: 3.29, 95%CI: 2.55-4.25) but a lower risk of death in hospital (aOR: 0.40, 95%CI: 0.33-0.49) as compared with non-frailty. Stratified analysis showed the impact of frailty on some of the outcomes were greater among patients younger than 65 years than their older counterparts. CONCLUSIONS: Frailty is significantly correlated with the increased risk of discharge to institutional care, tracheostomy or gastrostomy tube placement, and postoperative complications but with the reduced risk of in-hospital mortality outcomes after aneurysm repair. Frailty seems to have greater impact among younger adults than older ones. Baseline frailty evaluation could be applied to risk stratification for aSAH patients who were undergoing surgery.

Effects of dendrobium polysaccharides on human brain microvascular endothelial cell injury induced by ox-LDL via regulating the miR-378 expression.

Brain microvascular endothelial cells are a key part of the blood-brain barrier. This experiment was set up to investigate the effect and molecular mechanism of Dendrobium polysaccharide on oxidized low-density lipoprotein (ox-LDL)-induced damage to the human brain microvascular endothelial cells. For this purpose, human brain microvascular endothelial cells HBMEC were divided into control group (without any treatment), ox-LDL group (50 µg/mL ox-LDL), Dendrobium polysaccharide low, medium and high concentration group (0.1 µg/L, 0.2 µg/L, 0.4 µg/L Dendrobium polysaccharide+50 µg/mL ox-LDL), ox-LDL+miR-NC group (transfection miR-378 mimic negative control+50 µg/mL ox-LDL), ox-LDL+miR-378 group (transfected miR-378 mimics+50 µg/mL ox-LDL), ox-LDL+DP+anti-miR-NC group (transfected miR-378 inhibitor negative control +0.4 µg/L Dendrobium polysaccharide+50 µg/mL ox-LDL), ox-LDL+DP+anti-miR-378 group (transfected miR-378 inhibitor+0.4 µg/L Dendrobium polysaccharide+50 µg/mL ox-LDL ). The kit was used to detect the levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and catalase (CAT); flow cytometry to detect apoptosis; and Western blot to detect B-cell lymph tumor/leukemia-2 (Bcl-2) and Bcl-2 related X (Bax) protein expression; real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the expression of miR-378. Results showed that after treatment with different concentrations of Dendrobium polysaccharides, MDA levels were decreased in ox-LDL-induced human brain microvascular endothelial cells, SOD and CAT activities were increased, apoptosis rate was decreased, Bcl-2 expression was increased, Bax expression was decreased, miR-378 expression was increased, in a dose-dependent manner (P<0.05). Overexpression of miR-378 inhibits ox-LDL-induced oxidative stress and apoptosis in human brain microvascular endothelial cells. Inhibition of miR-378 expression reversed the effect of Dendrobium polysaccharide on ox-LDL-induced damage to human brain microvascular endothelial cells. Then dendrobium polysaccharide may inhibit ox-LDL-induced oxidative stress and apoptosis in human brain microvascular endothelial cells by up-regulating the expression of miR-378.

Palliative Interventional Embolization for Finding of Ectopic Noradrenaline-Secreting Pheochromocytoma in the Nasal Cavity.

A 52-year-old male who had chronic hypertension for several years presented with abrupt epistaxis. The CT scan revealed a 40 mm × 40 mm mass in the nasal cavity intended to the maxillary sinus and the base of skull. Nasal endoscope biopsy and serum/urinary catecholamine detection conformed an ectopic noradrenaline-secreting pheochromocytoma. The present research was to discuss the clinical characteristics of the rare pheochromocytoma and the palliative interventional embolization for it.

Regulation of Gli2 stability by deubiquitinase OTUB2.

The transcription factor Gli2 plays crucial roles in the transduction of Hedgehog (Hh) signals, yet the mechanisms that control Gli2 degradation remain unclear. Here we have identified the eubiquitinating enzyme otubain2 (OTUB2) as a regulator of Gli2 protein degradation. We found that OTUB2 was coimmunoprecipitated with Gli2. Knockdown of OTUB2 decreased Gli2 protein level while the proteasome inhibitor MG-132 treatment restored Gli2 expression. Additionally, OTUB2 overexpression stabilized Gli2 protein in U2OS cells and extended the half-life of Gli2. We also found that knockdown of OTUB2 reduced deubiquitination of Gli2 in vivo. In vitro deubiquitination assay showed that ubiquitinated Gli2 was decreased by wild-type OTUB2 but not OTUB2 mutations. We also found that OTUB2 knockdown suppressed the ALP activity and the expression of the common markers BMP2 and RUNX2 during osteogenesis of MSCs in response to Shh and Smo agonists, which indicated OTUB2 may have effect on osteogenic differentiation by regulating Hh signaling.

Ethyl Pyruvate Attenuates Early Brain Injury Following Subarachnoid Hemorrhage in the Endovascular Perforation Rabbit Model Possibly Via Anti-inflammation and Inhibition of JNK Signaling Pathway.

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is the main cause to poor outcomes of SAH patients, and early inflammation plays an important role in the acute pathophysiological events. It has been demonstrated that ethyl pyruvate (EP) has anti-inflammatory and neuroprotective effects in various critical diseases, however, the role of EP on EBI following SAH remains to be elucidated. Our study aimed to evaluate the effects of EP on EBI following SAH in the endovascular perforation rabbit model. All rabbits were randomly divided into three groups: sham, SAH + Vehicle (equal volume) and SAH + EP (30 mg/kg/day). MRI was performed to estimate the reliability of the EBI at 24 and 72 h after SAH. Neurological scores were recorded to evaluate the neurological deficit, ELISA kit was used to measure the level of tumor necrosis factor-α (TNF-α), and western blot was used to detect the expression of TNF-α, tJNK, pJNK, bax and bcl-2 at 24 and 72 h after SAH. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB) staining were used to detect neuronal apoptosis and neurodegeneration respectively, meanwhile hematoxylin and eosin (H&E) staining was used to assess the degree of vasospasm. Our results demonstrated that EP alleviated brain tissue injury (characterized by diffusion weighted imaging and T2 sequence in MRI scan), and significantly improved neurological scores at 72 h after SAH. EP decreased the level of TNF-α and downregulated pJNK/tJNK and bax/bcl-2 in cerebral cortex and hippocampus effectively both at 24 and 72 h after SAH. Furthermore, EP reduced TUNEL and FJB positive cells significantly. In conclusion, the present study supported that EP afforded neuroprotective effects possibly via reducing TNF-α expression and inhibition of the JNK signaling pathway. Therefore, EP may be a potent therapeutic agent to attenuate EBI following SAH.

5'-adenosine monophosphate-induced hypothermia attenuates brain ischemia/reperfusion injury in a rat model by inhibiting the inflammatory response.

Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5'-adenosine monophosphate (5'-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5'-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5'-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia.

Intracerebral arachnoid cyst treated with ommaya reservoir implantation in a patient younger than two years.

Intracranial arachnoid cysts are rare cystic-appearing intracranial masses. In rarer cases, the arachnoid cysts originate from brain parenchyma, which is defined as intracerebral arachnoid cyst. Here, we present a patient younger than 2 years with massive intracranial arachnoid cysts (one of which was intracerebral arachnoid cyst), whose clinical symptoms included megacephaly and limb weakness. Ommaya reservoir implantation and repeated aspiration of the intracerebral cyst fluid were performed. The symptoms gradually improved, and the intracerebral arachnoid cyst gradually disappeared during 13 months of follow-up. The case highlights the potential of Ommaya reservoir implantation in the treatment of intracerebral arachnoid cyst, especially for young patients. We also reviewed the published literatures concerning the rare condition, including the mechanisms for its pathogenesis and enlargement.

The diagnosis and surgical treatment of central brain herniations caused by traumatic bifrontal contusions.

The objective of this study was to investigate the diagnosis and surgical treatment of central brain herniations caused by traumatic bifrontal contusions. A total of 63 patients (45 men and 18 women; mean age of 43 years with a range from 20 to 72 years) who suffered from traumatic bifrontal contusions between January 2007 and December 2012 were inspected. The clinical and imaging results were studied for all patients, and we found that swelling of the mesencephalon and a downward shift of the bilateral red nucleus were significant signs of central brain herniation in the image of magnetic resonance imaging. All patients were given a simultaneous bilateral craniotomy for balanced decompressive surgery. The Glasgow Outcome Scale was used to monitor the patients during the follow-up period, which lasted from 6 to 52 months with a mean of 22 months. At the termination of the follow-up period, the following Glasgow Outcome Scale scores were obtained: 14 patients scored 5 points, 22 patients scored 4 points, 7 patients scored 3 points, 13 patients scored 2 points, and 7 patients scored 1 point. Therefore, our study suggested that an early magnetic resonance imaging scan could result in a more timely diagnosis of central brain herniation, and simultaneous bilateral craniotomy was found to be one of the best treatments for central brain herniation to improve patient outcomes.

Clinical features, angio-architectural phenotypes, and treatment strategy of foramen magnum dural arteriovenous fistulas: a retrospective case series study.

Background: The rarity and complex angioarchitecture of foramen magnum dural arteriovenous fistulas (DAVFs) make its treatment difficult and controversial. We aimed to describe their clinical features, angio-architectural phenotypes, and treatments, through a case series study. Methods: We first retrospectively studied cases of foramen magnum DAVFs treated in our Cerebrovascular Center, and then reviewed the published cases on Pubmed. The clinical characteristics, angioarchitecture, and treatments were analyzed. Results: A total of 55 patients were confirmed with foramen magnum DAVFs, which included 50 men and 5 women, with a mean age of 52.8 years. Most patients presented with subarachnoid hemorrhage (SAH) (21/55) or myelopathy (30/55), depending on the venous drainage pattern. In this group, 21 DAVFs were supplied by only the vertebral artery (VA), three by only the occipital artery (OA), three by only the ascending pharyngeal artery (APA), and the remaining 28 DAVFs were supplied by two or three of these feeding arteries. Most cases (30/55) were treated with only endovascular embolization, 18 cases (18/55) with only surgical disconnection, five cases (5/55) with combined therapy, and two cases rejected treatment. The angiographic outcome of complete obliteration was achieved in most patients (50/55). In addition, two cases of foramen magnum DAVFs were treated by us in a Hybrid Angio-Surgical Suite (HASS) with good outcomes. Conclusions: Foramen magnum DAVFs are rare and their angio-architectural features are complicated. The treatment option (microsurgical disconnection or endovascular embolization) should be weighed carefully, and combined therapy in HASS could be a more feasible and less invasive treatment option.

Innovative application of internal carotid artery embolization in salvage endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma: A case-matched comparison.

BACKGROUND: The efficacy and safety of internal carotid artery (ICA) embolization as a treatment strategy in recurrent nasopharyngeal carcinoma (rNPC) patients with tumors invading the ICA remain unclear. METHODS: We enrolled all rNPC patients with tumors invading the ICA, who underwent salvage endoscopic surgery. Using propensity scores to adjust for specific potential prognostic factors, a well-balanced cohort of 42 patients with limited rNPC was formed by matching each patient who underwent ICA embolization (study group) with one who did not (control group). The survival rates and common treatment-related complications were compared between the 2 groups. RESULTS: The cohort included patients with the following tumor stages: rT2 (n = 3), rT3 (n = 24), and rT4 (n = 15). During a median follow-up of 15 (range, 2-63) months, the 2-year overall survival and progression-free survival rates were significantly higher in the ICA embolization group than in the ICA nonembolization group (90.5% vs 53.3% and 71.3% vs 33.0%, respectively; and p = 0.022 and p = 0.006, respectively). In addition, the incidence of treatment-related complications, such as nasal obstruction, nasopharyngeal hemorrhage, and nasopharyngeal necrosis, was significantly lower in the ICA embolization group than in the nonembolization group (p = 0.001, p = 0.014, and p = 0.038, respectively). CONCLUSION: The innovative application of ICA embolization in endoscopic surgery in patients with rNPC invading the ICA significantly improved patient survival and reduced the risk of treatment-related complications. Therefore, this may be a safe and effective method with the potential to improve outcomes in rNPC patients.

Balloon Test Occlusion of Internal Carotid Artery in Recurrent Nasopharyngeal Carcinoma Before Endoscopic Nasopharyngectomy: A Single Center Experience.

OBJECTIVES: Endoscopic nasopharyngectomy (ENPG) is a promising way in treating recurrent nasopharyngeal carcinoma (rNPC), but sometimes may require therapeutic internal carotid artery (ICA) occlusion beforehand. Balloon test occlusion (BTO) is performed to evaluate cerebral ischemic tolerance for ICA sacrifice. However, absence of neurological deficits during BTO does not preclude occur of delayed cerebral ischemia after permanent ICA occlusion. In this study, we evaluate the utility of near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2) monitoring during ICA BTO to quantify cerebral ischemic tolerance and to identify the valid cut-off values for safe carotid artery occlusion. This study also aims to find out angiographic findings of cerebral collateral circulation to predict ICA BTO results simultaneously. MATERIAL AND METHODS: 87 BTO of ICA were performed from November 2018 to November 2020 at authors' institution. 79 angiographies of collateral flow were performed in time during BTO and classified into several Subgroups and Types according to their anatomic and collateral flow configurations. 62 of 87 cases accepted monitoring of cerebral rSO2. Categorical variables were compared by using Fisher exact tests and Mann-Whitney U tests. Receiver operating characteristic curve analysis was used to determine the most suitable cut-off value. RESULTS: The most suitable cut-off △rSO2 value for detecting BTO-positive group obtained through ROC curve analysis was 5% (sensitivity: 100%, specificity: 86%). NIRS rSO2 monitoring wasn't able to detect BTO false-negative results (p = 0.310). The anterior Circle was functionally much more important than the posterior Circle among the primary collateral pathways. The presence of secondary collateral pathways was considered as a sign of deteriorated cerebral hemodynamic condition during ICA BTO. In Types 5 and 6, reverse blood flow to the ICA during BTO protected patients from delayed cerebral ischemia after therapeutic ICA occlusion (p = 0.0357). In Subgroup IV, absence of the posterior Circle was significantly associated with BTO-positive results (p = 0.0426). CONCLUSION: Angiography of cerebral collateral circulation during ICA BTO is significantly correlated with ICA BTO results. Angiographic ICA BTO can be performed in conjunction with NIRS cerebral oximeter for its advantage of being noninvasive, real-time, cost-effective, simple for operation and most importantly for its correct prediction of most rSO2 outcomes of ICA sacrifice. However, in order to ensure a safe carotid artery occlusion, more quantitative adjunctive blood flow measurements are recommended when angiography of cerebral collateral circulation doesn't fully support rSO2 outcome among clinically ICA BTO-negative cases.

The mechanism of pathological changes of intraventricular hemorrhage in dogs.

BACKGROUND: Intraventricular hemorrhage (IVH) is an independent risk factor for both morbidity and mortality in patients with intracerebral hemorrhage and subarchnoid hemorrhage. The pathophysiological mechanisms by which blood within the ventricles causes brain damage are still poorly understood. SETTINGS AND DESIGN: We developed a canine (dog) model with long-term survival. AIMS: To study the mechanisms of pathological changes associated with IVH. MATERIALS AND METHODS: The neurological status, cranial computed tomographic findings, and the pathological changes were studied in the dogs with IVH and also in the control dogs, intraventiricular saline injection. RESULTS: In all the dogs in the control group there were no abnormalities in all the three parameters studied. The dogs in the IVH group developed neurological deficits after the blood injection. There was linear relationship between the ventricular volume and blood clot volume in the first week. After the first week, there was progressive enlargement of the ventricular volume, while the clots continued to shrink. There was complete lysis of the clots within 4 weeks. Pathological studies showed distruction of the ependymal lining of the ventricular system, subependymal gliosis and ischemia of the neurons in the subependymal areas, prominently around the aqueduct. CONCLUSION: Ventricular dilation was the prominent feature following intraventricular injection of the blood. The other pathological features included disruption of ependymal lining, subependymal gliosis, and ischemic necrosis of neurons in the periventricular tissue of the third ventricle, aqueduct, and the fourth ventricle. These pathological may have some role in the ventricular dilatation following IVH.

Ethyl pyruvate attenuates delayed experimental cerebral vasospasm following subarachnoid haemorrhage in rats: possible role of JNK pathway.

The pathophysiology of delayed cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH) is multifaceted and involves endothelial apoptosis and inflammation. Ethyl pyruvate (EP) could attenuate early brain injury following SAH via anti-inflammation and inhibition of the c-Jun N-terminal kinase (JNK) signalling pathway. However, the role of EP in the delayed CVS has yet to be determined. In this study, we examined the effect of EP on endothelial apoptosis and inflammation and explore possible signalling pathways. We found that EP could significantly attenuate the delayed CVS. Possible mechanisms include a decrease in the endothelial cell apoptosis of the basilar artery and alleviation of endothelial inflammation. The JNK signalling pathway may play an important role in the neuroprotective effects of EP on delayed CVS. The results suggest that EP may be a possible therapy for delayed CVS, and the JNK signalling pathway should be targeted for therapeutic purposes in the future.

Neuroprotective effect of baicalin on focal cerebral ischemia in rats.

Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin in a rat model of focal cerebral ischemia. Adult male Sprague-Dawley rat models of cerebral artery occlusion were established and then randomly and equally divided into three groups: ischemia (cerebral ischemia and reperfusion), valproic acid (cerebral ischemia and reperfusion + three intraperitoneal injections of valproic acid; positive control), and baicalin (cerebral ischemia and reperfusion + intraperitoneal injection of baicalin for 21 days). Neurological deficits were assessed using the postural reflex test and forelimb placing test at 3, 7, 14, and 21 days after ischemia. Rat cerebral infarct volume was measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining method. Pathological change of ischemic brain tissue was assessed using hematoxylin-eosin staining. In the baicalin group, rat neurological function was obviously improved, cerebral infarct volume was obviously reduced, and the pathological impairment of ischemic brain tissue was obviously alleviated compared to the ischemia group. Cerebral infarct volume was similar in the valproic acid and baicalin groups. These findings suggest that baicalin has a neuroprotective effect on cerebral ischemia.

Role of Microglia Autophagy in Microglia Activation After Traumatic Brain Injury.

OBJECTIVE: We evaluated the role of microglia autophagy in microglia activation after traumatic brain injury (TBI) in rats. METHODS: TBI was induced by a fluid percussion TBI device. All rats were killed 24 hours after TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin-eosin staining. Immunohistochemistry and Western blotting of ionized calcium-binding adapter molecule 1 was used to determine changes in microglia activation. Double staining of microtubule-associated protein light chain 3, Beclin-1, and ionized calcium-binding adapter molecule 1 was used to assess changes of microglia autophagy. Enzyme-linked immunosorbent assay of tumor necrosis factor-α and interleukin-1ß was used to evaluate changes in inflammatory responses. Terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick-end labeling staining was used to determine cell death in the ipsilateral hippocampus. RESULTS: At 24 hours after TBI, microglial cells became activated, and the autophagy inhibitor 3-methyladenine (3-MA) further promoted microglia activation. Protein light chain 3- and Beclin-1-positive microglial cells were increased after TBI, whereas 3-MA decreased the number of positive microglial cells, increasing the expression of tumor necrosis factor-α and interleukin-1ß; terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick-end labeling staining demonstrated that 3-MA could increase the number of terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick-end labeling-positive cells (16.83 ± 0.83 vs. 11 ± 0.82, P < 0.001). CONCLUSIONS: Our data demonstrated that TBI induced microglia activation and microglia autophagy. Inhibition of microglia autophagy with 3-MA increased microglia activation and neural apoptosis. These findings indicate that targeting microglia autophagy may be a therapeutic strategy for TBI.

Combination of early and delayed ischemic postconditioning enhances brain-derived neurotrophic factor production by upregulating the ERK-CREB pathway in rats with focal ischemia.

Ischemic postconditioning, including early and delayed ischemic postconditioning, has been recognized as a simple and promising strategy in the treatment of stroke. However, the effects of the combination of early and delayed ischemic postconditioning, and the mechanisms underlying these effects, remain unclear. The aim of the present study was to determine whether the combination of early and delayed ischemic postconditioning offers greater protection against stroke, and enhances the production of brain­derived neurotrophic factor (BDNF). A combination of early and delayed ischemic postconditioning was established by repeated, transient occlusion and reperfusion of the ipsilateral common carotid artery in a rat model of middle cerebral artery occlusion. Infarct size, motor function, cerebral blood flow and brain edema were then evaluated, in order to confirm the effects of combinative ischemic postconditioning. TUNEL staining was used to analyze the rate of apoptosis of cells in the penumbral area. BDNF, extracellular signal­regulated kinases 1/2 (ERK1/2) and cAMP response element­binding protein (CREB) expression was detected using immunofluorescence staining and western blot analysis. The results of the present study indicated that the combination of early and delayed ischemic postconditioning further reduced the infarct volume, stabilized cerebral blood disturbance and attenuated neuronal apoptosis, compared with either alone. However, combinative postconditioning exerted the same effect on neurological function and brain edema, compared with early or delayed ischemic postconditioning alone. Further investigation indicated that combinative ischemic postconditioning increased the expression of BDNF, and a significantly higher number of BDNF­positive cells was observed in neurons and astrocytes from the combined group than in the early or delayed groups. Combinative ischemic postconditioning also induced the phosphorylation of ERK1/2 and CREB in the cortex, following focal ischemia. The results of the present study suggest that the combination of early and delayed ischemic postconditioning may further reduce brain ischemic reperfusion injury following focal ischemia, compared with either treatment alone. In addition, it induces the production of BDNF in neurons and astrocytes. Furthermore, the effects of combinative ischemic postconditioning may be mediated by the activation of ERK1/2 and CREB.

Activations of GABAergic signaling, HSP70 and MAPK cascades are involved in baicalin's neuroprotection against gerbil global ischemia/reperfusion injury.

Baicalin, a flavonoid compound isolated from the plant Scutellaria baicalensis Georgi, is known as a protective agent against delayed neuronal cell death after ischemia/reperfusion. To investigate the neuroprotective mechanism of baicalin, the present study was conducted to explore whether the alterations of GABAergic signaling, heat shock protein 70 (HSP70) and mitogen-activated protein kinases (MAPKs) were involved in its neuroprotection on gerbils global ischemia. The bilateral carotid arteries were occluded by 5 min and baicalin at the dose of 200 mg/kg was intraperitoneally injected into the gerbils immediately after cerebral ischemia. Seven days after reperfusion, neurological deficit was scored and changes in hippocampal neuronal cell death were assessed by Nissl staining as well as NeuN immunohistochemistry. The mRNA and protein expressions of GABAergic signal molecules (GABA(A)R α1, GABA(A)R γ2, KCC2 and NKCC1) were determined in ischemic hippocampus by real-time RT-PCR and Western blot, respectively. In addition, HSP70 and MAPKs cascades (ERK, JNK and p38) were also detected using western blot assay. Our results illustrated that baicalin treatment significantly facilitated neurological function, suppressed the ischemia-induced neuronal damage. Besides, administration of baicalin also caused a striking increase of GABA(A)R α1, GABA(A)R γ2 and KCC2 together with the decrease of NKCC1 at mRNA and protein levels in gerbils hippocampus following an ischemic insult. Furthermore, the protein expressions of HSP70 and phosphorylated ERK (p-ERK) were evidently augmented while the phosphorylated JNK (p-JNK) and phosphorylated p38 (p-p38) were strikingly diminished in ischemic gerbils with baicalin treatment. These findings suggest that baicalin activates GABAergic signaling, HSP70 and MAPKs cascades in global ischemia, which may be a mechanism underlying the baicalin's neuroprotection.

Migration of neural stem cells to ischemic brain regions in ischemic stroke in rats.

An established rat model of ischemic stroke, produced by temporary middle cerebral artery occlusion and reperfusion (MCAO/R), was used in the evaluation of organ migration of intra-arterial (IA) transplantation of neural stem cells (NSCs). Immediately after transplantation, ischemic rats (n=8) transplanted with either NSCs (MCAO/R+NSC group) or NSC growth medium (MCAO/R+medium group) exhibited neurological dysfunction but rats in a sham+NSCs group (n=5) did not. During the post-operative period, neurological function improved to a similar extent in both MCAO/R groups. At 10 and 14 days post-transplantation, neurological function in the MCAO/R+NSC group was superior to that in the MCAO/R+medium group (p<0.001). Hematoxylin-eosin staining showed neuronal degeneration and necrosis in ischemic rats. Immunofluorescence staining revealed that NSCs had migrated to the frontal and parietal lobes, caudate, and putamen. Some cells had begun differentiating into neurons and astrocytes. Rat NSCs can migrate into the ischemic region, survive, and differentiate into astrocytes and neurons, and thereby potentially improve neurologic function after cerebral ischemia.