Functional brain mapping based on changes in local cerebral blood flow (lCBF) or glucose utilization (lCMRglc) induced by functional activation is generally carried out in animals under anesthesia, usually ␣-chloralose because of its lesser effects on cardiovascular, respiratory, and reflex functions. Results of studies on the role of nitric oxide (NO) in the mechanism of functional activation of lCBF have differed in unanesthetized and anesthetized animals. NO synthase inhibition markedly attenuates or eliminates the lCBF responses in anesthetized animals but not in unanesthetized animals. The present study examines in conscious rats and rats anesthetized with ␣-chloralose the effects of vibrissal stimulation on lCMRglc and lCBF in the whisker-to-barrel cortex pathway and on the effects of NO synthase inhibition with N G -nitro-L-arginine methyl ester (L-NAME) on the magnitude of the responses. Anesthesia markedly reduced the lCBF and lCMRglc responses in the ventral posteromedial thalamic nucleus and barrel cortex but not in the spinal and principal trigeminal nuclei. L-NAME did not alter the lCBF responses in any of the structures of the pathway in the unanesthetized rats and also not in the trigeminal nuclei of the anesthetized rats. In the thalamus and sensory cortex of the anesthetized rats, where the lCBF responses to stimulation had already been drastically diminished by the anesthesia, L-NAME treatment resulted in loss of statistically significant activation of lCBF by vibrissal stimulation. These results indicate that NO does not mediate functional activation of lCBF under physiological conditions. whisker-to-barrel cortex pathway ͉ cerebral glucose utilization ͉ deoxy[ 14 C]glucose ͉ functional brain imaging ͉ iodo[ 14 C]antipyrine N euronal functional activation is normally associated with increases in local cerebral glucose utilization (lCMR glc ) and blood flow (lCBF) in anatomic units of the activated neural pathways. These associations are now widely exploited to map regions of the brain involved in specific neural and cognitive processes. The mechanisms underlying the functional activation of lCMR glc are reasonably well understood. Glucose utilization is increased by functional activation in direct proportion to the increases in spike frequency in the afferent inputs to the activated areas, and the increases are localized in neuropil and not perikarya (1, 2). The increases in lCMR glc appear to result mainly from activation of Na ϩ ,K ϩ -ATPase activity (2, 3), needed to restore ionic gradients in the neuronal elements degraded by the spike activity. Neuropil contains not only axonal and dendritic processes but also astroglial processes, and glutamate stimulates glucose utilization in astroglia, also due in part to activation of Na ϩ ,K ϩ -ATPase activity by coupled uptake of Na ϩ ions with the glutamate released during functional activation (4, 5). Glucose utilization is also increased to support the ATPdependent conversion to glutamine of the glutamate taken up by the astroglia (6).The mechan...

Lipopolysaccharide (LPS), administered 72 hours before middle cerebral artery (MCA) occlusion, confers significant protection against ischemic injury. For example, in the present study, LPS (0.9 mg/kg intravenously) induced a 31% reduction in infarct volume (compared with saline control) assessed 24 hours after permanent MCA occlusion. To determine whether LPS induces true tolerance to ischemia, or merely attenuates initial ischemic severity by augmenting collateral blood flow, local CBF was measured autoradiographically 15 minutes after MCA occlusion. Local CBF did not differ significantly between LPS- and saline-pretreated rats (e.g., 34 +/- 10 and 29 +/- 15 mL x 100 g(-1) x min(-1) for saline and LPS pretreatment in a representative region of ischemic cortex), indicating that the neuroprotective action of LPS is not attributable to an immediate reduction in the degree of ischemia induced by MCA occlusion, and that LPS does indeed induce a state of ischemic tolerance. In contrast to the similarity of the initial ischemic insult between tolerant (LPS-pretreated) and nontolerant (saline-pretreated) rats, microvascular perfusion assessed either 4 hours or 24 hours after MCA occlusion was preserved at significantly higher levels in the LPS-pretreated rats than in controls. Furthermore, the regions of preserved perfusion in tolerant animals were associated with regions of tissue sparing. These results suggest that LPS-induced tolerance to focal ischemia is at least partly dependent on the active maintenance of microvascular patency and hence the prevention of secondary ischemic injury.

Early decompressive craniectomy with duroplasty before the onset of brain herniation should be performed to achieve satisfactory functional recovery if the infarct volume of the hemispheric cerebral infarction is more than 200 cm(3) and computed tomography on the second day after the ictus shows mass effect.