prostaglandin-d2 and Brain-Infarction

To investigate the effect of PPARγ agonist 15d-PGJ2 treatment on the microglia activation and neurological deficit of ischemia reperfusion in diabetic rat model, adult Sprague-Dawley rats were sacrificed for the research. The rats were randomly categorized into four groups: (1) sham-operated group; (2) standard ischemia group; (3) diabetic ischemia group; (4) diabetic ischemia group with diabetes and treated with 15d-PGJ2. Compared to the sham-operated group, all the ischemic groups have significantly severer neurological deficits, more TNF-α and IL-1 expression, increased labeling of apoptotic cells, increased CD68 positive staining of brain lesion, and increased volume of infarct and cerebral edema in both 24 hours and 7 days after reperfusion. Interestingly, reduced neurological deficits, decreased TNF-α and IL-1 expression, less apoptotic cells and CD68 positive staining, and alleviated infarct and cerebral edema volume were observed when 15d-PGJ2 was intraperitoneally injected after reperfusion in diabetic ischemia group, suggesting its neuroprotective role in regulating microglia activation, which may have a therapeutic application in the future.

Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Apoptosis; Brain Edema; Brain Infarction; Diabetes Mellitus, Experimental; Interleukin-1; Microglia; PPAR gamma; Prostaglandin D2; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tumor Necrosis Factor-alpha

The neuroprotective effects and mechanism of action of GIF-0173, a Delta12-prostaglandin J analogue, were investigated in the early phase of cerebral ischemia. GIF-0173 was administered intravenously immediately following middle cerebral artery occlusion (MCAO) in photochemically induced thrombosis model of rat. Neurological scores and infarct sizes were examined at 24 h after MCAO. Cerebral blood flow (CBF) was monitored by laser-Doppler flowmetry for 1 h after MCAO. In cultured cortical neurons obtained from 1-day-old rats, the effects of GIF-0173 on the excitotoxicity induced by glutamate were examined. Morphological changes, neuronal death, and changes in intracellular calcium concentration ([Ca(2+)](i)) were also examined. GIF-0173 improved neurological scores and reduced the infarct size in a dose-dependent manner following MCAO. But GIF-0173 did not improve CBF after MCAO. GIF-0173 also prevented glutamate-induced neuronal death and acute cellular swelling in primary cultures in a dose-dependent manner, indicating that it inhibited neuronal necrosis. GIF-0173 dose-dependently suppressed the glutamate-induced increase in [Ca(2+)](i), but could not inhibit NMDA-induced calcium influx. The effects of GIF-0173 against glutamate-induced [Ca(2+)](i) increase were reversed by addition of non-specific prostaglandin D (PGD(2)) receptor antagonist and were comparable to the effects of PGD(2) DP1 receptor agonist, which prevented [Ca(2+)](i) increase and neuronal death. We conclude that GIF-0173 reduces cerebral infarction and protects cultured neurons against glutamate-induced excitotoxicity by inhibiting [Ca(2+)](i) increase through DP1 receptor activation.

Topics: Animals; Brain Infarction; Calcium; Cell Death; Cells, Cultured; Cerebral Cortex; Cerebrovascular Circulation; Dantrolene; Disease Models, Animal; Dose-Response Relationship, Drug; Glutamic Acid; Hydantoins; Infarction, Middle Cerebral Artery; Intracellular Fluid; Lactones; Laser-Doppler Flowmetry; Male; N-Methylaspartate; Neurons; Neuroprotective Agents; Platelet Aggregation Inhibitors; Prostaglandin D2; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Immunologic; Receptors, Prostaglandin; Sesquiterpenes; Severity of Illness Index; Tetrazolium Salts