Temporal profile of the effects of pretreatment with brief cerebral ischemia on the neuronal damage following secondary ischemic insult in the gerbil: cumulative damage and protective effects

The xanthine derivative propentofylline (HWA 285) has been reported to show protective effects against neuronal damage induced by cerebral ischemia. In the present study, microfluorometry was used to investigate the effect of propentofylline on the hypoxia–hypoglycemia-induced intracellular calcium accumulation in gerbil hippocampal slices. When slices were superfused with hypoxic–hypoglycemic medium that did not contain propentofylline, an acute increase in calcium accumulation was detected 75–200 s (mean latency of 123 s) after the beginning of hypoxia–hypoglycemia. When slices were superfused with hypoxic–hypoglycemic mediums that contained 10 μ M, 100 μ M, and 1 m M propentofylline, the latency of the acute increase in calcium accumulation was prolonged in all subregions of the hippocampus in a dose-dependent manner: mean latencies in field CA1 were 146, 168, and 197 s after hypoxia–hypoglycemia, respectively. This retardation in calcium accumulation may be involved in the mechanisms by which propentofylline diminishes ischemic injury.

Download Full-text

Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/470975 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 14

Author(s):

Zun-Jing Liu ◽

Wei Liu ◽

Lei Liu ◽

Cheng Xiao ◽

Yu Wang ◽

...

Keyword(s):

Cerebral Ischemia ◽

Neuronal Damage ◽

Infarct Volume ◽

Critical Role ◽

Ischemic Injury ◽

Ppar Gamma ◽

Neurological Deficits ◽

Protective Effects ◽

Cerebral Ischemic Injury ◽

Cerebral Ischemic

Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPARγagonist in that it upregulated PPARγexpression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγinteracted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγinduced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.

Download Full-text

Proteomic Assessment of iTRAQ-Based NaoMaiTong in the Treatment of Ischemic Stroke in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/5107198 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Kening Li ◽

Minghua Xian ◽

Chi Chen ◽

Shengwang Liang ◽

Lei Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Cerebral Ischemia ◽

Cerebral Infarction ◽

Western Blot ◽

Stress Responses ◽

Neuronal Damage ◽

Interaction Analysis ◽

Protective Effects ◽

Cellular Mechanisms ◽

Altered Expression

Background. NaoMaiTong (NMT) is widely used in the treatment of cerebral ischemia but the molecular details of its beneficial effects remain poorly characterized. Materials and Methods. In this study, we used iTRAQ using 2D LC-MS/MS technology to investigate the cellular mechanisms governing the protective effects of NMT. The transient middle cerebral artery occlusion (MCAO) rat model was established and evaluated. The degree of cerebral ischemia was assessed through scoring for nerve injury symptoms and through the assessment of the areas of cerebral infarction. Brain tissues were subjected to analysis by iTRAQ. High-pH HPLC and RSLC-MS/MS analysis were performed to detect differentially expressed proteins (DEPs) between the treatment groups (Sham, MCAO, and NMT). Bioinformatics were employed for data analysis and DEPs were validated by western blot. Results. The results showed that NMT offers protection to the neurological damage caused by MCAO and was found to reduce the areas of cerebral infarction. We detected 3216 DEPs via mass spectrometry. Of these proteins, 21 displayed altered expression following NMT intervention. These included DEPs involved in translation, cell cycle regulation, cellular nitrogen metabolism, and stress responses. Pathway analysis revealed seven key DEPs that were enriched in ribosomal synthesis pathways, tight junction formation, and regulation of the actin cytoskeleton. According to protein-protein interaction analysis, RPL17, Tuba, and Rac1 were affected by NMT treatment, which was validated by western blot analysis. Discussion. We therefore identify new pharmacodynamic mechanisms of NMT for the prevention and treatment of ischemic stroke. These DEPs reveal new targets to prevent ischemic stroke induced neuronal damage.

Download Full-text

Neuroprotective effects of adenosine deaminase in the striatum

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x15625077 ◽

2016 ◽

Vol 36 (4) ◽

pp. 709-720 ◽

Cited By ~ 7

Author(s):

Risa Tamura ◽

Hiroyuki Ohta ◽

Yasushi Satoh ◽

Shigeaki Nonoyama ◽

Yasuhiro Nishida ◽

...

Keyword(s):

Cerebral Ischemia ◽

Adenosine Deaminase ◽

Neuronal Damage ◽

Brain Slices ◽

Field Potential ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

Protective Effects ◽

Neuroprotective Effects ◽

Negative Effect

Adenosine deaminase (ADA) is a ubiquitous enzyme that catabolizes adenosine and deoxyadenosine. During cerebral ischemia, extracellular adenosine levels increase acutely and adenosine deaminase catabolizes the increased levels of adenosine. Since adenosine is a known neuroprotective agent, adenosine deaminase was thought to have a negative effect during ischemia. In this study, however, we demonstrate that adenosine deaminase has substantial neuroprotective effects in the striatum, which is especially vulnerable during cerebral ischemia. We used temporary oxygen/glucose deprivation (OGD) to simulate ischemia in rat corticostriatal brain slices. We used field potentials as the primary measure of neuronal damage. For stable and efficient electrophysiological assessment, we used transgenic rats expressing channelrhodopsin-2, which depolarizes neurons in response to blue light. Time courses of electrically evoked striatal field potential (eFP) and optogenetically evoked striatal field potential (optFP) were recorded during and after oxygen/glucose deprivation. The levels of both eFP and optFP decreased after 10 min of oxygen/glucose deprivation. Bath-application of 10 µg/ml adenosine deaminase during oxygen/glucose deprivation significantly attenuated the oxygen/glucose deprivation-induced reduction in levels of eFP and optFP. The number of injured cells decreased significantly, and western blot analysis indicated a significant decrease of autophagic signaling in the adenosine deaminase-treated oxygen/glucose deprivation slices. These results indicate that adenosine deaminase has protective effects in the striatum.

Download Full-text

MK-801 (Dizocilpine) Protects the Brain from Repeated Normothermic Global Ischemic Insults in the Rat

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1993.115 ◽

1993 ◽

Vol 13 (6) ◽

pp. 925-932 ◽

Cited By ~ 31

Author(s):

Baowan Lin ◽

W. Dalton Dietrich ◽

Myron D. Ginsberg ◽

Mordecai Y.-T. Globus ◽

Raul Busto

Keyword(s):

Cerebral Ischemia ◽

Repeated Measures ◽

Neuronal Damage ◽

Brain Temperature ◽

Global Cerebral Ischemia ◽

Striatal Neurons ◽

Ischemic Insult ◽

Mk 801 ◽

Bilateral Carotid ◽

Ventrolateral Thalamus

We investigated the neuroprotective potential of MK-801 (dizocilpine), a noncompetitive N-methyl-d-aspartate (NMDA) antagonist, in the setting of three 5-min periods of global cerebral ischemia separated by 1-h intervals in halothane-anesthetized rats. Each ischemic insult was produced by bilateral carotid artery occlusions plus hypotension (50 mm Hg). Brain temperature was maintained at normothermic levels (36.5–37.0°C) throughout the experiment. MK-801 (3 mg/kg) (n = 6) or saline (n = 6) was injected intraperitoneally 45 min following the end of the first ischemic insult. Following 7-day survival, quantitative neuronal counts of perfusion-fixed brains revealed severe ischemic damage in hippocampal CA1 area, neocortex, ventrolateral thalamus, and striatum of untreated rats. By contrast, significant protection was observed in MK-801-treated rats. In area CA1 of the hippocampus, numbers of normal neurons were increased 11- to 14-fold by MK-801 treatment (p < 0.01). The ventrolateral thalamus of MK-801-treated rats showed almost complete histologic protection, and neocortical damage was reduced by 71% (p < 0.01). The degree of MK-801 protection of striatal neurons was less complete than that seen in other vulnerable structures, amounting to 63% for central striatum (p = 0.02, Mann–Whitney U test) and 48% in the dorsolateral striatum (NS). A repeated-measures analysis of variance demonstrated a highly significant overall protective effect of MK-801 treatment ( F1,10 = 37.2, p = 0.0001). These findings indicate that excitotoxic mechanisms play a major role in neuronal damage produced by repeated ischemic insults and that striking cerebroprotection is conferred by MK-801 administered following the first insult in animals with cerebral normothermia. NMDA antagonists may prove useful in patients at risk of repeated episodes of cerebral ischemia.

Download Full-text