Vasoactive arachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. In order to characterize the local generation of cyclooxygenase and lipoxygenase metabolites of arachidonic acid in transient ischemia with reperfusion, Mongolian gerbils were studied for regional cerebral blood flow (CBF), using the hydrogen clearance technique, and for cerebral levels of the thromboxane metabolite TXB2, and prostaglandins 6-keto-PGF1 alpha and PGE2, as well as the leukotriene LTB4. The gerbils were anesthetized with pentobarbital, and half of the animals were pretreated with the cyclooxygenase inhibitor indomethacin. All received 10 or 20 minutes of dense forebrain ischemia followed by reperfusion of 10 minutes, 50 minutes, or 100 minutes. A separate control group received no ischemic lesion. Regional CBF decreased significantly from 23.7 +/- 2.6 to 4.3 +/- 1.7 cc/100 gm/min during ischemia (p less than 0.01). Reperfusion resulted in initially normal flows (22.5 +/- 5.1 cc/100 gm/min) followed by a progressive hypoperfusion (11.3 +/- 2.7 cc/100 gm/min). All metabolites showed parallel significant (p less than 0.05) increases after transient ischemia and reperfusion compared to baseline levels (values (in pg/mg protein) were: TXB2 45.5 +/- 7.1 vs 23.3 +/- 3.6; 6-keto-PGF1 alpha 262.8 +/- 47.9 vs 175.8 +/- 26.8; PGE2 256.5 +/- 35.6 vs 112.5 +/- 11.2; and LTB4 37.8 +/- 4.6 vs 24.6 +/- 6). These levels were all significantly decreased (p less than 0.05) by pretreatment with indomethacin except for the leukotriene LTB4, which was increased. Transient cerebral ischemia results in a reperfusion abnormality and the local generation of cyclooxygenase products, which are reduced by pretreatment with indomethacin; however, cyclooxygenase inhibition may result in increased substrate availability for the lipoxygenase system. Studies of such an interaction may lead to new understandings of the pharmacological modification of detrimental vascular changes after transient cerebral ischemia.

Using the bilateral carotid artery occlusion model of cerebral ischemia in the gerbil, we studied the effect of moderate hypothermia (30 to 31 degrees C) on the postischemic production of prostanoids (cyclooxygenase pathway) and leukotrienes (lipoxygenase pathway) and accompanying changes in cerebral edema formation. Hypothermia capable of slowing central evoked potential conduction time was studied over the course of 40 minutes of cerebral ischemia and for up to 2 hours of reperfusion. The successful induction of cerebral ischemia was confirmed by somatosensory evoked potential amplitude changes. Measurements of 6-ketoprostaglandin F1 alpha (PGF1 alpha) and leukotriene B4 (LTB4) (radioimmunoassay) and cerebral edema (specific gravity) were made at early (10 minutes) and late (2 hours) reperfusion times. Although both white and gray matter showed no early significant difference in edema accumulation between normothermic and hypothermic gerbils at 10 minutes of reperfusion, hypothermic animals demonstrated significantly less white matter edema (specific gravity, 1.0397 +/- 0.0010 vs. 1.0341 +/- 0.0012, P less than 0.01) and gray matter edema (specific gravity, 1.0408 +/- 0.0009 vs. 1.0365 +/- 0.0008, P less than 0.01) by 2 hours of reperfusion. Production of PGF1 alpha was not significantly different between normothermic and hypothermic animals during the reperfusion period; however, hypothermic gerbils demonstrated significantly lower production of LTB4 at 10 minutes reperfusion time compared to normothermic animals (1.49 +/- 0.79 vs. 5.28 +/- 1.49 pg/mg of protein, P less than 0.05). This difference between the two groups in LTB4 levels was no longer detectable at 2 hours of reperfusion time.(ABSTRACT TRUNCATED AT 250 WORDS)

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Somatosensory evoked potentials (SEP's) reflect the integrity of the central neuronal pathway, and as such may be used to assess function that remains during a variety of cerebral insults. To evaluate the natural history and utility of SEP's during experimental cerebral ischemia and infarction, SEP's were measured in 17 adult cats at 24 hours and 1 hour prior to right middle cerebral artery (MCA) occlusion, and again immediately afterward and at either 6 hours (five cats) or 24 hours (six cats) post-occlusion. Before occlusion of the right MCA, the SEP's were identical in the right and left hemispheres. After occlusion, there was a significant slowing of the interpeak latency of the first positive peak (P1) in the right hemisphere (3.53 +/- 0.6 msec before compared to 3.99 +/- 0.6 msec after occlusion, p less than 0.001). Maximal slowing in right hemisphere P1 latency was seen in those animals in which the stroke extended into the thalamus (4.38 +/- 0.1 msec). This was significantly slower than left hemisphere values (3.92 +/- 0.32 msec, p less than 0.01). The ipsilateral cortical components of the SEP's, the second positive peak (P2), and the major negative deflection (MN) were slowed in all cats immediately after right MCA occlusion compared to preocclusion measurements (p less than 0.001). Severe infarcts in the mid-suprasylvian and posterior ectosylvian gyri (including the somatosensory cortex) resulted in a greater slowing of the latency of MN compared to less severe infarcts in that region (20.6 +/- 3.9 msec versus 16.4 +/- 1.1 msec, p less than 0.05). There was a precipitous decrease in the amplitude or voltage of the ipsilateral P2-MN complex immediately after occlusion (5.32 +/- 0.4 microV before compared to 0.98 +/- 0.3 microV after occlusion, p less than 0.001). Therefore, the central latencies and cortical amplitudes of the SEP's are sensitive experimental tools as indicators of the onset and extent of a cerebral ischemic insult.