Summary: It was shown previously that focal cortical freezing lesions in rats cause widespread decrease in local cerebral glucose utilization (LCGU) in cortical areas of the lesioned hemisphere. This was interpreted as reflecting a depression of cortical activity. It was then demonstrated that cortical serotonin (5-HT) metabolism was increased throughout the lesioned hemisphere of a focally injured brain. To find out if the changes in the serotonergic system are of functional importance and me diate the observed changes in LCG U, the effects of the inhibition of 5-HT synthesis with p-chlorophenylalanine (PCP A) on cerebral metabolism and biogenic amine con tent in injured brain were studied. PCPA in doses up to 300 mg/kg had little, if any, effect on LCG U in intact brain and in doses up to 100 mg/kg did not modify the depressed LCGU in injured brain. In doses of 200 and 300 mg/kg, PCP A selectively increased cortical glucose utilization in the lesioned hemisphere where it was de pressed following injury. PCPA decreased 5-HT levels in U sing focal cortical freezing in the rat as a model of cerebral injury and the deoxyglucose (DG) method as developed and described by Sokoloff et al. (1977) to assess the functional state of trauma tized brain, earlier studies (Pappius, 1981) showed that a widespread, but not uniformly distributed, depression of local cerebral glucose utilization Abbreviations used: DG, deoxyglucose; DHBA, dihydroxy benzylamine; 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, sero tonin; LCGU, local cerebral glucose utilization; NE, norepi nephrine; PCPA, p-chlorophenylalanine . 324the cortical and raphe areas of both intact and injured brain in a dose-dependent manner. However, at doses of PCPA ineffective on LCGU (50 and 100 mg/kg), traumati zation still resulted in increased 5-HT metabolism. Doses of PCPA that ameliorated the depression of LCGU in in jured brain completely prevented increases in both 5-HT and its metabolite 5-hydroxyindoleacetic acid seen fol lowing traumatization in untreated animals. These results provide evidence that decreased LCGU in lesioned brain is due to an activation of the serotonergic system by trau matization. The data are in agreement with the postulated inhibitory role of serotonin in the cortex and its involve ment in functional alterations associated with injury. They suggest that blockage of this neurotransmitter system may have a potential in the development of novel therapeutic approaches to brain injury. Key Words: Brain injury-p-Chlorophenylalanine-Local cerebral glucose utilization -Norepinephrine -Serotonin.(LCGU ) developed with time after lesioning. The effects were not related to the location of the le sion, which was regularly placed in the parietal cortex, but could be made more frontally or cau dally with the same results (Colle et aI., 1986). The most severe metabolic depression occurred in all the cortical regions of the lesioned hemisphere were 3 days after the lesion LCGU was -50% of normal from frontal to visual cortex (Pappius, 198 1). Thus, the ...

It was shown previously that focal cortical freezing lesions in rats cause widespread depression of local cerebral glucose utilization (LCGU) in cortical areas of the lesioned hemisphere. This was interpreted as reflecting functional depression. The underlying mechanisms were postulated to involve alterations of biogenic amine systems. Accordingly, levels of serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5-HIAA), and its precursor tryptophan were determined by an HPLC method with electrochemical detection in frontoparietal cortical areas of both hemispheres at 4 h and 1, 3, 6, 8, and 10 days after a unilateral cortical freezing lesion. The 5-HT content was significantly lower than normal in the lesioned hemisphere only at 24 h, whereas the 5-HIAA level peaked at 24 h but was significantly elevated above normal values between 4 h and 6 days after lesioning. No changes were noted in 5-HT and 5-HIAA contents in the hemisphere contralateral to the lesion. These results indicate that cortical 5-HT metabolism is increased throughout the lesioned hemisphere of a focally injured brain. The increase in tryptophan content of the lesioned brain appeared to have a time course more closely related to previously demonstrated changes in cortical LCGU than to the increase in 5-HIAA content.