Fibroblast Growth Factor-18 Reduced Infarct Volumes and Behavioral Deficits After Transient Occlusion of the Middle Cerebral Artery in Rats

Ellsworth, Jeff L.; Garcia, Richard U.; Yu, Jin; Kindy, Mark S.

doi:10.1161/01.str.0000071760.66720.5f

Cited by 45 publications

(34 citation statements)

References 29 publications

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“…As mentioned above, previous results suggest that the endothelin system is affected even at 2 days after 2 h of MCAO while infarct size could be reduced by administration of ET A receptor antagonist at similar time points (Matsuo et al, 2001). In addition, the findings that various agents can decrease cerebral infarct size after 2 h of MCAO with 22-h reperfusion (Endres et al, 1998;Ellsworth et al, 2003) suggest that such ischemia-induced brain injury can still be reversed. Cerebral edema is also present 24 h after 2 h MCAO (Yang et al, 1992).…”

Section: Introductionmentioning

confidence: 84%

Endothelin-1 Overexpression Leads to Further Water Accumulation and Brain Edema after Middle Cerebral Artery Occlusion via Aquaporin 4 Expression in Astrocytic End-Feet

Chen

Hung

et al. 2005

J Cereb Blood Flow Metab

133

156

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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.

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Section: Introductionmentioning

confidence: 84%

Endothelin-1 Overexpression Leads to Further Water Accumulation and Brain Edema after Middle Cerebral Artery Occlusion via Aquaporin 4 Expression in Astrocytic End-Feet

Chen

Hung

et al. 2005

J Cereb Blood Flow Metab

133

156

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“…Strategies to limit infarct volume in animal models of ischemic stroke using growth factors and transplantation of stem cells have shown functional benefits. 214,215 Similar utilization of stem cells delivered by a variety of routes to the residual hematoma cavity and administration of growth factors may potentiate the restorative capacity of the human brain leading to improved functional outcome.…”

Section: Delayed Restorative Surgical Proceduresmentioning

confidence: 99%

Priorities for Clinical Research in Intracerebral Hemorrhage

Morgenstern

Woodbury-Harris²,

Marler³

2005

Stroke

119

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“…The findings that various agents can decrease cerebral infarct size after 2 h of middle cerebral artery occlusion (MCAO) with 22-h reperfusion (Ellsworth et al, 2003;Endres et al, 1998a) suggest that such ischemia-induced brain injury can still be reversed. Cerebral edema is also present 24 h after 2 h of MCAO (Yang et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Deletion of Aldose Reductase Leads to Protection against Cerebral Ischemic Injury

Cheung

Hung

et al. 2007

J Cereb Blood Flow Metab

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Previously, we reported that transgenic mice overexpressing endothelin-1 in astrocytes showed more severe neurological deficits and increased infarct after transient focal ischemia. In those studies, we also observed increased level of aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, which has been implicated in osmotic and oxidative stress. To further understand the involvement of the polyol pathway, the mice with deletion of enzymes in the polyol pathway, AR, and sorbitol dehydrogenase (SD), which is the second enzyme in this pathway, were challenged with similar cerebral ischemic injury. Deletion of AR-protected animals from severe neurological deficits and large infarct, whereas similar protection was not observed in mice with SD deficiency. Most interestingly, AR À/À brains showed lowered expression of transferrin and transferrin receptor with less iron deposition and nitrotyrosine accumulation. The protection against oxidative stress in AR À/À brain was also associated with less poly(adenosine diphosphate-ribose) polymerase (PARP) and caspase-3 activation. Pharmacological inhibition of AR by Fidarestat also protected animals against cerebral ischemic injury. These findings are the first to show that AR contributes to iron-and transferrin-related oxidative stress associated with cerebral ischemic injury, suggesting that inhibition of AR but not SD may have therapeutic potential against cerebral ischemic injury.

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Fibroblast Growth Factor-18 Reduced Infarct Volumes and Behavioral Deficits After Transient Occlusion of the Middle Cerebral Artery in Rats

Abstract: These results demonstrate that FGF18 is an effective neuroprotective agent in a rat model of transient MCAo.

Cited by 45 publications

References 29 publications

Endothelin-1 Overexpression Leads to Further Water Accumulation and Brain Edema after Middle Cerebral Artery Occlusion via Aquaporin 4 Expression in Astrocytic End-Feet

Endothelin-1 Overexpression Leads to Further Water Accumulation and Brain Edema after Middle Cerebral Artery Occlusion via Aquaporin 4 Expression in Astrocytic End-Feet

Priorities for Clinical Research in Intracerebral Hemorrhage

Deletion of Aldose Reductase Leads to Protection against Cerebral Ischemic Injury

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