Effect of Tianhuang Granule on intracranial pressure and serum matrix metalloproteinase-9 in patients with acute cerebral hemorrhage.
ABSTRACT To study the effect and mechanism of Tianhuang Granule (, THG) on: hydrocephalus in the patients with acute cerebral hemorrhage (ACH) through intracranial pressure (ICP) monitoring, serum matrix metalloproteinase-9 (MMP-9) level observation, and National Institutes of Health Stroke Scale (NIHSS) scoring (for nerve function de ficit).
Sixty patients with ACH were equally randomized: into two groups by lottery, the control group and the THG group; all were treated with conventional therapy, but to the patients in the THG group, THG was given orally in addition for 28 days. Changes of ICP, MMP-9 expression, and NIHSS scores, as well as the degree of cerebral hematoma and hydrocephalus (by cranial CT scanning) in the patients, were estimated and compared.
(1) ICP was lowered more significantly in the: THG group, showing a significant difference between groups on day 7 (P<0.05). (2) MMP-9 expression was down-regulated in the THG group more significantly and earlier than that in the control group. (3) The degrees of cerebral hematoma and hydrocephalus in the THG group on day 7 were reduced significantly as compared with those on day 3 (P<0.05), but in the control group, the day of significant reduction was delayed to day 14, and the degrees on day 7 and day 14 in the two groups were significantly different (P<0.05 and P<0.01). (4) NIHSS score was significantly lower in the THG group than that in the control group on day 14 and day 28 (P<0.05 and P<0.01).
THG can effectively lower ICP, down-regulate MMP-9 expression, promote the absorption: of cerebral hematoma and hydrocephalus, and improve the nerve function, showing a clinical effectiveness than conventional therapy.
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ABSTRACT: Stroke patients have increased levels of endothelin-1 (ET-1), a strong vasoconstrictor, in their plasma or cerebrospinal fluid. Previously, we showed high level of ET-1 mRNA expression in astrocytes after hypoxia/ischemia. It is unclear whether the contribution of ET-1 induction in astrocytes is protective or destructive in cerebral ischemia. Here, we generated a transgenic mouse model that overexpress ET-1 in astrocytes (GET-1) using the glial fibrillary acidic protein promoter to examine the role of astrocytic ET-1 in ischemic stroke by challenging these mice with transient middle cerebral artery occlusion (MCAO). Under normal condition, GET-1 mice showed no abnormality in brain morphology, cerebrovasculature, absolute cerebral blood flow, blood-brain barrier (BBB) integrity, and mean arterial blood pressure. Yet, GET-1 mice subjected to transient MCAO showed more severe neurologic deficits and increased infarct, which were partially normalized by administration of ABT-627 (ET(A) antagonist) 5 mins after MCAO. In addition, GET-1 brains exhibited more Evans blue extravasation and showed decreased endothelial occludin expression after MCAO, correlating with higher brain water content and increased cerebral edema. Aquaporin 4 expression was also more pronounced in astrocytic end-feet on blood vessels in GET-1 ipsilateral brains. Our current data suggest that astrocytic ET-1 has deleterious effects on water homeostasis, cerebral edema and BBB integrity, which contribute to more severe ischemic brain injury.Journal of Cerebral Blood Flow & Metabolism 09/2005; 25(8):998-1011. · 5.34 Impact Factor
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ABSTRACT: Abnormal expression of some matrix metalloproteinases (MMP) has shown to play a deleterious role in brain injury in experimental models of cerebral ischemia. We aimed to investigate MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in brain parenchyma in both ischemic and hemorrhagic strokes. Postmortem fresh brain tissue from 6 ischemic and 8 hemorrhagic stroke patients was obtained within the first 6 hours after death. Finally, 78 brain tissue samples from different areas (infarct, peri-infarct, perihematoma and contralateral hemisphere) were studied. To quantify gelatinase content we performed gelatin zymograms that were confirmed by Western Blot Analysis, immunohistochemistry to localize MMP source, and in situ zymography to detect gelatinase activity. Among ischemic cases, gelatin zymography showed increased MMP-9 content in infarct core although peri-infarct tissue presented also higher levels than contralateral hemisphere (P<0.0001 and P=0.042, respectively). Within infarct core, MMP-9 was mainly located around blood vessels, associated to neutrophil infiltration and activated microglial cells. In peri-infarct areas the major source of MMP-9 were microglial cells. Tissue around intracranial hemorrhage also displayed higher MMP-9 levels than contralateral hemisphere (P=0.008) in close relationship with glial cells. MMP-2 was constitutively expressed and remained invariable in different brain areas. Our results demonstrate in situ higher levels of MMP-9 in human brain tissue after ischemic and hemorrhagic stroke, suggesting a contribution of MMP-9 to ischemic brain injury and perihematoma edema.Stroke 07/2006; 37(6):1399-406. · 6.02 Impact Factor
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ABSTRACT: We aimed to determine the severity and pattern of cognitive dysfunction in patients with basal ganglia (BG) hemorrhage within the first 6 months after stroke and to identify its clinical correlates. The study samples consisted of 30 patients with BG hemorrhage and 37 healthy controls. A comprehensive neuropsychological battery including tests of attention, memory, language, visuospatial function, and executive function was administered to all participants. Relative to healthy controls, BG patients performed significantly worse across different cognitive domains after controlling for age, sex, and education. 96.7% of patients displayed defective performance on at least three neuropsychological tests. Discriminant function analysis showed that visuospatial function and memory were the best predictors of group membership (patient/control), with an overall classification rate of 95.5%. Only side of stroke and admission Glasgow Coma Scale (GCS) score correlated significantly with some of the cognitive domains. The widespread pattern of cognitive deficits seen in BG patients provides evidence for the substantial involvement of the BG in many neuronal pathways connecting cortical and subcortical brain areas responsible for various cognitive functions.Archives of Clinical Neuropsychology 06/2007; 22(4):465-74. · 1.92 Impact Factor