UNASSIGNED: There is currently a lack of evidence in evidence-based medicine regarding acupuncture treatment for experimental intracerebral hemorrhage (ICH). The aim of this study was to systematically evaluate the efficacy of acupuncture treatment for experimental ICH based on neurological function scores and brain water content (BWC).
UNASSIGNED: Eight mainstream Chinese and English databases were searched. Outcome measures included neurological function scores and BWC, and subgroup analysis was conducted based on study characteristics.
UNASSIGNED: A total of 32 studies were included. Meta-analysis results indicated that compared to the control group, the acupuncture group showed significant reductions in mNSS (MD = -3.16, p < 0.00001), Bederson score (MD = -0.99, p < 0.00001), Longa score (MD = -0.54, p < 0.0001), and brain water content (MD = -5.39, p < 0.00001). Subgroup analysis revealed that for mNSS, the autologous blood model (MD = -3.36) yielded better results than the collagenase model (MD = -0.92, p < 0.00001), and simple fixation (MD = -3.38) or no fixation (MD = -3.39) was superior to sham acupuncture (MD = -0.92, p < 0.00001). For BWC, the autologous blood model (MD = -7.73) outperformed the collagenase model (MD = -2.76, p < 0.00001), and GV20-GB7 (MD = -7.27) was more effective than other acupuncture points (MD = -2.92, p = 0.0006).
UNASSIGNED: Acupuncture significantly improves neurological deficits and brain edema in experimental ICH. Acupuncture at GV20 - GB7 is more effective than at other points. These findings support further studies to translate acupuncture into clinical treatment for human ICH.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42023435584.

Context: Hypoxia-inducible factor-1α (HIF-1α)-induced genes can improve blood circulation.Objective: To investigate brain protective effect of recombinant adenovirus-mediated HIF-1α (AdHIF-1α) expression and its mechanism.Materials and methods: Male SD rats were used to establish focal cerebral ischaemia-reperfusion (CIR) injury models and randomly divided into normal, sham, CIR, Ad and AdHIF-1α groups. Ad or AdHIF-1α (108 pfu/10 µL) were administered into lateral ventricle of rats in Ad and AdHIF-1α groups. Modified neurological severity score (mNSS), brain water content (BWC) and cerebral infarct volumes (CIVs) were analyzed, and HE staining was performed using the brain tissues. Furthermore, the expression of caspase-3 and HSP90 was analyzed using qRT-PCR and Western blotting.Results: Compared to CIR (mNSS, 8.52 ± 0.52; CIV, 0.22 ± 0.01) and Ad groups (mNSS, 8.83 ± 0.41; CIV, 0.22 ± 0.02), mNSS and CIV were significantly decreased in AdHIF-1α group (mNSS, 6.03 ± 0.61; CIV, 0.11 ± 0.01) at 72 h (p < 0.05). With prolonged reperfusion time (6 h to 72 h), BWC of all rats increased gradually, although the increase was markedly less in AdHIF-1α group (78.15 ± 0.16 to 87.01 ± 0.31) compared to that in CIR (78.77 ± 0.60 to 89.74 ± 0.34) and Ad groups (78.77 ± 0.35 to 89.71 ± 0.27) (p < 0.01). There were significantly greater pathological changes in the neurons in AdHIF-1α group at 72 h following CIR. Furthermore, expression of caspase-3 (p < 0.01) down-regulated and HSP90 up-regulated (p < 0.05) at mRNA and protein levels in AdHIF-1α group.Discussion and conclusions: HIF‑1α gene therapy is neuroprotective towards the CIR rat model. HIF-1α may be a candidate gene for the treatment of ischaemic brain injury.

Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive. The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome has been postulated to mediate inflammation during SAH. The aim of the present study was to investigate the effects of caspase-8 inhibition on SAH injury and further elucidate the molecular mechanisms. In this study, a subarachnoid hemorrhage model was established by endovascular perforation process in adult male Sprague-Dawley rats. Z-IETD-FMK (0.5, 1, 2 mg/kg; an inhibitor of caspase-8) was delivered via intravenous (tail vein) injection immediately after subarachnoid hemorrhage. After 12 hours of subarachnoid hemorrhage, western blot assay showed that the expression of cleaved caspase-8 was significantly increased at 12 hours, peaked at 24 hours, and then decreased at 72 hours after subarachnoid hemorrhage. Immunofluorescence staining demonstrated that caspase-8 was expressed in microglia after subarachnoid hemorrhage. Z-IETD-FMK significantly improved neurological deficits and reduced brain water content 24 hours after subarachnoid hemorrhage. The Morris water maze and rotarod test confirmed that Z-IETD-FMK significantly improved spatial learning and memory abilities and motor coordination at 21-27 days after subarachnoid hemorrhage. Furthermore, inhibition of caspase-8 activation reduced the expression of pyrin domain-containing 3, caspase-1, and interleukin-1β after subarachnoid hemorrhage. In conclusion, our findings suggest that caspase-8 inhibition alleviates subarachnoid hemorrhage-induced brain injuries by suppressing inflammation. The study was approved by the Institutional Animal Ethics Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University, China (approval No. 2016-193) on February 25, 2016.

BACKGROUND: Cerebral venous infarction (CVI) is a rare vascular disease most commonly caused by cerebral venous thrombosis that leads to hemorrhage or infarct formation. A rabbit model of CVI was established by placing a recoverable epidural sacculus to research effects of increased pressure on CVI.
METHODS: Rabbits were randomly divided into the following groups: A, CVI; B, 0.2-mL epidural sacculus placed on the basis of CVI; C, 0.4-mL epidural sacculus; D, 0.6-mL epidural sacculus; E, sham operation. Two sacculus-release groups were then added, 8 hours (group F) and 24 hours (group G), on the basis of group D. Brain water content, extent of cerebral infarction, hemorheology indexes, D dimer, and fibrinogen were observed at 8, 24, and 48 hours after surgery.
RESULTS: Brain water content was higher in groups A-D compared with group E with the exception of the 24-hour A group. Brain water content was significantly lower in sacculus-release groups compared with the 48-hour D group. Extent of cerebral infarction in group D was significantly higher at 24 and 48 hours compared with groups A and E. Extent of cerebral infarction in sacculus-release groups was significantly lower compared with group D at 48 hours. Hemorheology indexes and fibrinogen were significantly higher in group D compared with groups A and E at corresponding time points and increased with increasing intracranial pressure.
CONCLUSIONS: In the rabbit model of CVI, degree of brain edema, extent of cerebral infarction, hemorheology indexes, and fibrinogen increased as intracranial pressure gradient increased, which may promote formation of a hypercoagulable state. Early removal of intracranial hypertension reduced degree of edema and extent of cerebral infarction in rabbits.

This study aimed to explore the role and mechanism(s) of flunarizine hydrochloride in the intracerebral hemorrhage (ICH) rats. The 32 adult male Sprague Dawley (SD) rats were randomly assigned into four groups: control group, sham group, ICH group, and FLU + ICH group. The effects of flunarizine hydrochloride were assessed on the basis of hematoma volume, blood-brain barrier (BBB) integrity, and brain water content in the ICH rat models. The role of flunarizine hydrochloride in cell recovery was assessed by behavioral scores, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot assay. Involvement of PI3K/AKT pathway in exerting the effect of flunarizine hydrochloride was also determined. Results showed that the hematoma volume, BBB integrity, and brain water content were significantly decreased in the FLU + ICH group. Cell apoptosis significantly increased in the ICH model group, while flunarizine hydrochloride decreased this increase. The expressions of glial cell line-derived neurotrophic factor (GDNF), neuroglobin (NGB), and p-AKT were increased after flunarizine hydrochloride treatment in ICH rats. In conclusion, flunarizine hydrochloride has protective effects against ICH by reducing brain injury, cell apoptosis, and the activation of P13K/AKT pathway. These findings provide a theoretical basis for the treatment of flunarizine hydrochloride in ICH.

BACKGROUND: There are numerous potential treatments assessed for acute cerebral ischemia using animal models. This study aimed to assess the effect of these treatments in terms of infarct size and neurobehavioral change. This meta-analysis was conducted to determine if any of these treatments provide a superior benefit so that they might be used on humans.
METHODS: A systematic search was conducted using several electronic databases for controlled animal studies using only nonsurgical interventions for acute cerebral ischemia. A random-effects model was used.
RESULTS: After an extensive literature search, 145 studies were included in the analysis. These studies included 1408 treated animals and 1362 control animals. Treatments that had the most significant effect on neurobehavioral scales included insulin, various antagonists, including N-methyl-D-aspartate (NMDA) receptor antagonist ACEA1021, calmodulin antagonist DY-9760e, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist YM872, and antiviral agents. Treatments providing the greatest effect on infarct size included statins, sphingosine-1-phosphate agonist (fingolimod), alcohol, angiotensin, and leukotrienes. Treatments offering the greatest reduction in brain water content included various agonists, including sphingosine-1-phosphate agonist fingolimod, statins, and peroxisome proliferator-activated receptor gamma (PPAR-γ). Treatment groups with more than one study all had high heterogeneity (I2 > 80%), however, using meta-regression we determined several sources of heterogeneity including sample size of the treatment and control groups, the occlusion time, but not the year when the study was conducted.
CONCLUSIONS: Some treatments stand out when compared to others for acute cerebral ischemia in animals. Greater replication of treatment studies is required before any treatments are selected for future human trials.

The adipocytokine, apelin-13, is an abundantly expressed peptide in the nervous system. Apelin-13 protects the brain against ischemia/reperfusion injury and attenuates traumatic brain injury by suppressing autophagy. However, secondary apelin-13 effects on traumatic brain injury-induced neural cell death and blood-brain barrier integrity are still not clear. Here, we found that apelin-13 significantly decreases cerebral water content, mitigates blood-brain barrier destruction, reduces aquaporin-4 expression, diminishes caspase-3 and Bax expression in the cerebral cortex and hippocampus, and reduces apoptosis. These results show that apelin-13 attenuates secondary injury after traumatic brain injury and exerts a neuroprotective effect.

Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points (20 μL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury.

Dl-3n-butylphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. Dl-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es-timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier age and cerebral edema.

Oxidative damage plays a detrimental role in the pathophysiology of cerebral ischemia and may represent a therapeutic target. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) controls the coordinated expression of the important antioxidant and detoxification genes through a promotor sequence termed the antioxidant response element. Bicyclol has been proved to elicit a variety of biological effects through its antioxidant and anti-inflammatory properties. But the underlying mechanisms are poorly understood. In this study, the role of bicyclol in cerebral ischemia and its potential mechanism were investigated.
METHODS: Male Sprague-Dawley rats were randomly assigned to five groups: MCAO (middle cerebral artery occlusion), Vehicle (MCAO+0.5% sodium carboxymethylcellulose), By-L (Vehicle+bicyclol 50mg/kg), By-H (Vehicle+bicyclol 100mg/kg) and Sham operated groups. Bicyclol was administered intragastrically once a day for 3 consecutive days; after 1h of bicyclol pretreatment on the third day, rat ischemic stroke was induced by MCAO. Neurological deficit, infarct volume, and brain edema were detected at 24h after stroke. Western blot and RT-qPCR were used to measure the expression of Nrf2, HO-1 and SOD1. MDA was detected by the spectrophotometer.
RESULTS: Compared with MCAO group, By-H group significantly ameliorated neurological deficit, lessened the infarct volume and brain edema, increased the expression of Nrf2, HO-1 and SOD1 (P<0.05), and decreased the content of MDA (P<0.05).
CONCLUSIONS: Bicyclol protected the rat brain from ischemic damage caused by MCAO, and this effect may be through the upregulation of the transcription factor Nrf2 expression.