Cortical Neurogenesis in Adult Rats after Reversible Photothrombotic Stroke

Neurogenesis occurs throughout life in the dentate gyrus of hippocampus and subventricular zone, but this phenomenon has rarely been observed in other brain regions of adult mammals. The aim of the current study was to investigate the cell proliferation process in the ischemically challenged region-at-risk after focal cerebral ischemia in the adult rat brain. A reversible photothrombotic ring stroke model was used, which features sustained hypoperfusion followed by late spontaneous reperfusion and a remarkable morphologic tissue recovery in the anatomically well defined somatosensory cortical region-at-risk. Twelve-week-old male Wistar rats received repeated intraperitoneal injections of the cell proliferation specific marker 5-bromodeoxyuridine (BrdU) after stroke induction. Immunocytochemistry of coronal brain sections revealed that the majority of BrdU-positive cells were of glial, macrophage, and endothelial origin, whereas 3% to 6% of the BrdU-positive cells were double-labeled by BrdU and the neuron-specific marker Map-2 at 7 and 100 days after stroke onset in the region-at-risk. They were distributed randomly in cortical layers II-VI. Three-dimensional confocal analyses of BrdU and the neuronal-specific marker Neu N by double immunofluorescence confirmed their colocalization within the same cells at 72 hours and 30 days after stroke induction. This study suggests that, as a potential pathway for brain repair, new neurons can be generated in the cerebral cortex of adult rats after sublethal focal cerebral ischemia.

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Cell proliferation in ependymal/subventricular zone and nNOS expression following focal cerebral ischemia in adult rats

Neurological Research ◽

10.1179/016164106x91942 ◽

2006 ◽

Vol 28 (1) ◽

pp. 91-96 ◽

Cited By ~ 15

Author(s):

Pengbo Zhang ◽

Yong Liu ◽

Jie Li ◽

Qianyan Kang ◽

Yingfang Tian ◽

...

Keyword(s):

Cell Proliferation ◽

Cerebral Ischemia ◽

Subventricular Zone ◽

Focal Cerebral Ischemia ◽

Adult Rats ◽

Nnos Expression

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Three-dimensional structure and survival of newly formed blood vessels after focal cerebral ischemia

Neuroreport ◽

10.1097/00001756-200306110-00014 ◽

2003 ◽

Vol 14 (8) ◽

pp. 1171-1176 ◽

Cited By ~ 47

Author(s):

Jerzy Krupinski ◽

Paul Stroemer ◽

Mark Slevin ◽

Eulalia Marti ◽

Pat Kumar ◽

...

Keyword(s):

Cerebral Ischemia ◽

Blood Vessels ◽

Focal Cerebral Ischemia ◽

Three Dimensional ◽

Dimensional Structure ◽

Three Dimensional Structure

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Increased expression of suppressor of cytokine signaling 2 in the subventricular zone after transient focal cerebral ischemia in adult rats

Brain Research ◽

10.1016/j.brainres.2016.07.040 ◽

2016 ◽

Vol 1648 ◽

pp. 163-171 ◽

Cited By ~ 1

Author(s):

Yoo-Jin Shin ◽

Tae-Ryong Riew ◽

Xuyan Jin ◽

Jeong-Heon Choi ◽

Mun-Yong Lee

Keyword(s):

Cerebral Ischemia ◽

Subventricular Zone ◽

Focal Cerebral Ischemia ◽

Cytokine Signaling ◽

Suppressor Of Cytokine Signaling ◽

Adult Rats ◽

Transient Focal Cerebral Ischemia

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Abstract 196: Sanguinate (PEGylated-carboxyhemoglobin-bovine) Improves Cerebral Blood Flow and Oxygen Extraction to Vulnerable Brain Regions in Patients at Risk for Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Stroke ◽

10.1161/str.48.suppl_1.196 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Rajat Dhar ◽

Hemant Misra ◽

Michael Diringer

Keyword(s):

At Risk ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Delayed Cerebral Ischemia ◽

Brain Regions ◽

Oxygen Extraction ◽

Patients At Risk ◽

Higher Doses

Introduction: Sanguinate is a dual-action oxygen transfer and carbon monoxide-releasing agent with efficacy in animal models of focal brain ischemia and established safety in health volunteers. We performed a dose-escalation study in subarachnoid hemorrhage (SAH) patients at risk for delayed cerebral ischemia (DCI) to evaluate tolerability and explore efficacy in improving cerebral blood flow (CBF) and flow-metabolism balance to vulnerable brain regions. Methods: 12 subjects were studied over three dose tiers: 160mg/kg, 240 mg/kg, and 320 mg/kg, with close safety evaluation prior to proceeding to higher doses. After baseline 15 O-PET measurement of global and regional CBF and oxygen extraction fraction (OEF), Sanguinate was infused over two hours; PET was repeated immediately after and again at 24-hours. Vulnerable brain regions were defined as those with baseline OEF ≥ 0.5. Results: Sanguinate infusion resulted in a significant but transient rise in mean arterial pressure (115±15 to 127±13 mm Hg) that was not dose-dependent. No adverse physiologic or clinical effects were observed with infusion at any dose. Global CBF did not rise significantly after Sanguinate (42.6±7 to 45.9±9 ml/100g/min, p=0.18). However, in the 28% of regions classified as vulnerable, Sanguinate resulted in a significant rise in CBF (42.2±11 to 51.2±18) and reduction in OEF (0.6±0.1 to 0.5±0.11, both p<0.001). The increase in regional CBF was only seen with the two higher doses but OEF improved in all tiers. However, response was attenuated at 24-hours. Conclusions: We safely administered a novel oxygen transport and vasodilating agent to a cohort of patients with SAH. Sanguinate infusion appeared to improve CBF and flow-metabolism balance in vulnerable brain regions and warrants further study in those at-risk for DCI. Higher or repeat dosing may be required for sustained efficacy.

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Xanthine oxidase is not a major source of free radicals in focal cerebral ischemia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.260.2.h563 ◽

1991 ◽

Vol 260 (2) ◽

pp. H563-H568 ◽

Cited By ~ 1

Author(s):

A. L. Betz ◽

J. Randall ◽

D. Martz

Keyword(s):

Uric Acid ◽

Free Radicals ◽

Cerebral Ischemia ◽

Xanthine Oxidase ◽

Brain Edema ◽

Focal Cerebral Ischemia ◽

Total Activity ◽

Brain Regions ◽

Free Radical Scavengers ◽

Edema Formation

Xanthine oxidase (XO) has been proposed as an important source of free radicals during ischemia. This enzyme normally exists as a dehydrogenase (XD), but it is converted to XO in some ischemic tissues. Recently, treatment of animals with the XD and XO inhibitor allopurinol or with free radical scavengers before cerebral ischemia has been shown to reduce brain injury. Therefore, we studied conversion of XD to XO in three ischemic and nonischemic brain regions during focal cerebral ischemia resulting from permanent occlusion of the middle cerebral artery (MCAO) in anesthetized rats. In nonischemic brain, 16-22% of the enzyme was in the XO form. After 24 h of ischemia this value was not significantly different (10-15%). Neither the total activity of XO nor that of XD changed, indicating that there was no irreversible conversion of XD to XO. To further explore the possible role of XO, we examined the effect of various doses of allopurinol (5, 20, or 100 mg/kg given 1 h before MCAO or 100 mg/kg given 48, 24, and 1 h before MCAO) on uric acid accumulation, brain edema formation, and cerebral blood flow (CBF) 24 h after MCAO. All but the lowest dose of allopurinol greatly reduced the appearance of uric acid in the ischemic brain; however, only the highest dose of allopurinol had any beneficial effect on brain edema. This reduction in brain edema occurred without a significant improvement in CBF. Thus XO is probably not an important source of free radicals in this model of focal cerebral ischemia.

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