scholarly journals Thresholds in cerebral ischemia - the ischemic penumbra.

Stroke ◽  
1981 ◽  
Vol 12 (6) ◽  
pp. 723-725 ◽  
Author(s):  
J Astrup ◽  
B K Siesjö ◽  
L Symon
Keyword(s):  
Cerebral Ischemia ◽  
Ischemic Penumbra

scholarly journals Tissue Acidosis Associated with Ischemic Stroke to Guide Neuroprotective Drug Delivery

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 460
Author(s):  
Orsolya M. Tóth ◽  
Ákos Menyhárt ◽  
Rita Frank ◽  
Dóra Hantosi ◽  
Eszter Farkas ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Targeted Delivery ◽  
Focal Cerebral Ischemia ◽  
Ischemic Penumbra ◽  
Risk Of Injury ◽  
Ischemic Tissue ◽  
Tissue Acidosis ◽  
Injury Progression

Ischemic stroke is a leading cause of death and disability worldwide. Yet, the effective therapy of focal cerebral ischemia has been an unresolved challenge. We propose here that ischemic tissue acidosis, a sensitive metabolic indicator of injury progression in cerebral ischemia, can be harnessed for the targeted delivery of neuroprotective agents. Ischemic tissue acidosis, which represents the accumulation of lactic acid in malperfused brain tissue is significantly exacerbated by the recurrence of spreading depolarizations. Deepening acidosis itself activates specific ion channels to cause neurotoxic cellular Ca2+ accumulation and cytotoxic edema. These processes are thought to contribute to the loss of the ischemic penumbra. The unique metabolic status of the ischemic penumbra has been exploited to identify the penumbra zone with imaging tools. Importantly, acidosis in the ischemic penumbra may also be used to guide therapeutic intervention. Agents with neuroprotective promise are suggested here to be delivered selectively to the ischemic penumbra with pH-responsive smart nanosystems. The administered nanoparticels release their cargo in acidic tissue environment, which reliably delineates sites at risk of injury. Therefore, tissue pH-targeted drug delivery is expected to enrich sites of ongoing injury with the therapeutical agent, without the risk of unfavorable off-target effects.

Enriched environment and spatial learning enhance hippocampal neurogenesis and salvages ischemic penumbra after focal cerebral ischemia

2006 ◽  
Vol 22 (1) ◽  
pp. 187-198 ◽  
Author(s):  
Yasuhiko Matsumori ◽  
Shwuhuey M. Hong ◽  
Yang Fan ◽  
Takamasa Kayama ◽  
Chung Y. Hsu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Spatial Learning ◽  
Focal Cerebral Ischemia ◽  
Hippocampal Neurogenesis ◽  
Enriched Environment ◽  
Ischemic Penumbra

scholarly journals Effects of S-312-d on cerebral microcirculation in ischemic penumbra in rat focal cerebral ischemia

1996 ◽  
Vol 71 ◽  
pp. 235
Author(s):  
Takefumi Gemba ◽  
Mitsuyoshi Ninomiya ◽  
Kazuo Umemura ◽  
Mitsuyoshi Nakashima
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Ischemic Penumbra ◽  
Cerebral Microcirculation

Abstract W MP75: Docosahexaenoic Acid Upregulates Iduna Expression in the Ischemic Penumbra and Protects Rat Brains Against Focal Ischemia

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Nicolas G Bazan ◽  
Pranab K Mukherjee ◽  
Veronica Balaszczuk ◽  
Larissa Khoutorova ◽  
Daniela V Anzola ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Docosahexaenoic Acid ◽  
Western Blot ◽  
Time Course ◽  
Ring Finger ◽  
Blood Gases ◽  
Glutamate Excitotoxicity ◽  
Experimental Stroke ◽  
Ischemic Penumbra ◽  
Arterial Blood

Introduction: Ring finger protein 146, also called Iduna, has been identified, as a neuroprotective protein. Iduna facilitates DNA repair and protects against cell death induced by NMDA receptor-mediated glutamate excitotoxicity or cerebral ischemia. Recently, we have shown that docosahexaenoic acid (DHA; 22:6n-3) therapy improves functional and histological outcomes following experimental stroke. This study evaluated the time course expression of Iduna in the ischemic penumbra and the role of DHA in cerebral ischemia and its potential mechanism. METHODS: Thirty-six male SD rats were anesthetized with isoflurane and subjected to 2 h of middle cerebral artery occlusion (MCAo) by poly-L-lysine-coated intraluminal suture. DHA (5 mg/kg) or vehicle (saline) was administered IV at 3 h after the onset of MCAo and animals were sacrificed on days 1, 3 and 7 (n=6 rats per group). The neurological function was evaluated during occlusion (60 min), and on days 1, 3 and 7 after MCAo; a grading scale of 0-12 was employed (0=normal and 12=maximal deficit). Western blot and double immunostaining (Iduna/NeuN and Iduna/GFAP) were used to analyze Iduna expression in the ischemic penumbra on days 1, 3 and 7. RESULTS: All animals showed similar values for rectal and cranial temperatures, arterial blood gases, and plasma glucose during and after MCAo. Behavioral deficit was significantly improved by treatment with DHA compared to vehicle on days 1 (by 30%), 3 (by 31%) and 7 (by 32%). Western-blot analysis showed that DHA treatment increased Iduna expression in the ischemic penumbra compared to vehicle on day 1 (2.2±0.3 vs. 0.6±0.1) and day 3 (0.44±0.05 vs. 0.3±0.01, respectively). There were no differences in Iduna expression on day 7 between DHA and vehicle-treated groups (0.33±0.02 and 0.35±0.02). Immunostaining revealed that Iduna expression was increased in the penumbra of DHA-treated rats. Conclusions: DHA protected the brain from severe damage caused by MCAo. This effect may be through upregulation of Iduna expression in the ischemic penumbra. Thus, it is reasonable to hypothesize that DHA has potential for the effective treatment of ischemic stroke in patients.

Induction of tolerance against ischemia/reperfusion injury in the rat brain by preconditioning with the endotoxin analog diphosphoryl lipid A

2000 ◽  
Vol 92 (3) ◽  
pp. 435-441 ◽  
Author(s):  
Tomikatsu Toyoda ◽  
Neal F. Kassell ◽  
Kevin S. Lee
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Lipid A ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Penumbra ◽  
Sod Activity ◽  
Content Type ◽  
Fine Print

Object. Inflammatory responses and oxygen free radicals have increasingly been implicated in the development of ischemic brain injury. In some cases, an attenuation of inflammation or free-radical injury can provide tissue protection. Diphosphoryl lipid A (DPL) is a detoxified derivative of a lipopolysaccharide (endotoxin) of Salmonella minnesota strain R595, which is capable of stimulating the immune system without eliciting direct toxic effects. In this study the authors examined the influence of preconditioning with DPL on ischemia/reperfusion injury in rats.Methods. Sprague—Dawley rats were injected intravenously with either DPL or vehicle. Twenty-four hours later, some animals were tested for superoxide dismutase (SOD) activity. Others were subjected to a 3-hour period of focal cerebral ischemia and, after a reperfusion period of 24 hours, were killed. Infarction volume, SOD activity, and myeloperoxidase (MPO) activity were assayed in the postischemic animals.Pretreatment with DPL produced significant reductions in cerebral infarction and MPO activity in the ischemic penumbra. A significant enhancement of basal SOD activity was observed 24 hours after DPL treatment (that is, before ischemia), and a further enhancement of SOD activity was seen in the ischemic penumbra 24 hours after reperfusion.Conclusions. These data provide the first evidence of a neuroprotective effect of preconditioning with DPL in an in vivo model of cerebral ischemia. Although the precise mechanisms through which DPL exerts its neuroprotective influence remain to be established, an inhibition of the complex inflammatory response to ischemia and an enhancement of endogenous antioxidant activity are leading candidates.

Abstract TP268: Induction Profile of Mesencephalic Astrocyte-derived Neurotrophic Factor by Cerebral Ischemia and its Implication for Neuroprotection

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Ludmila Belayev ◽  
Sung-Ha Hong ◽  
Pranab K Mukherjee ◽  
Hemant Menghani ◽  
Larissa Khoutorova ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Dentate Gyrus ◽  
Mrna Expression ◽  
Neurotrophic Factor ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Ischemic Penumbra ◽  
Protein Levels

Introduction: Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been identified as a secretion protein, which biases immune cells toward an anti-inflammatory phenotype, thereby promoting tissue repair after various injuries to neurons in vivo or in vitro. However, the function of MANF during and after brain ischemia is still not known. The purpose of our study was to examine the characteristics and implication of MANF expression induced by focal cerebral ischemia. In addition we investigated if docosahexaenoic acid (DHA) potentiates MANF mRNA expression and provides additional neuroprotection. Methods: Male SD (280-320) rats were anesthetized with isoflurane and subjected to 2 h of middle cerebral artery occlusion (MCAo) by intraluminal suture. DHA (5 mg/kg; n=13) or vehicle (saline; n=8) was administered IV at 3 h after the onset of MCAo. Neurological function was evaluated during occlusion (60 min) and on days 1, 3 and 7 after MCAo. MANF mRNA expression, protein levels, and apoptosis were measured by immunohistochemistry and Western blotting. Results: Behavioral deficit was significantly improved by treatment with DHA compared to vehicle on days 1, 3 and 7. MANF was found to be extremely upregulated in the ischemic penumbra. The expression of MANF was neuronal in the cortex and dentate gyrus. DHA administration significantly increased the number of MANF + /NeuN + cells in the cortex (by 76.6 %) and dentate gyrus (by 20.5 %) compared to saline-treated animals. The number of MANF/NeuN-positive cells was not different in the subcortex, CA1 and CA3 regions between DHA- and saline-treated groups. Treatment with DHA increased MANF + /GFAP + cells in the subcortex (by 27.7 %) and dentate gyrus (by 38.0 %) compared to the vehicle-treated brains. Total and cortical infarct volumes were attenuated by DHA treatment by 48 % and by 73 % compared to vehicle treatment at 24 h after MCAo. Conclusion: MANF mRNA expression and protein levels are increased after focal cerebral ischemia. It was found to be extremely upregulated in the ischemic penumbra and dentate gyrus. The expression of MANF was mostly neuronal and astrocytic. DHA potentiates MANF expression and provides additional neuroprotection.

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