Changes in regional cerebral blood flow (rCBF) and glucose metabolism are commonly associated with traumatic brain injury (TBI). Reactive oxygen species (ROS) have been implicated as key contributors to the secondary injury process after TBI. Here, pretreatment with the nitrone radical scavengers (alpha-phenyl-N-tert-butyl nitrone (PBN) or its sulfonated analogue sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) were used as tools to study the effects of ROS on rCBF and glucose metabolism after moderate (2.4-2.6 atm) lateral fluid percussion injury (FPI) in rats. S-PBN has a half-life in plasma of 9 min and does not penetrate the blood-brain barrier (BBB). In contrast, PBN has a half-life of 3 h and readily penetrates the BBB. Regional cerebral blood flow (rCBF) and glucose metabolism was estimated by using (99m)Tc-HMPAO and [(18)F]Fluoro-2-deoxyglucose (FDG) autoradiography, respectively, at 42 min (n = 37) and 12 h (n = 34) after the injury. Regions of interest were the parietal cortex and hippocampus bilaterally. As expected, FPI produced an early (42-min) hypoperfusion in ipsilateral cortex and an increase in glucose metabolism in both cortex and hippocampus, giving way to a state of hypoperfusion and decreased glucose metabolism at 12 h postinjury. On the contralateral side, a hypoperfusion in the cortex and hippocampus was seen at 12 h only, but no significant changes in glucose metabolism. Both S-PBN and PBN attenuated the trauma-induced changes in rCBF and glucose metabolism. Thus, the early improvement in rCBF and glucose metabolism correlates with and may partly mediate the improved functional and morphological outcome after TBI in nitrone-treated rats.
Adult rats were subjected to a moderate lateral¯uid percussion injury (FPI), followed by survival periods of 2 and 12 h. Regional NMDA subtype glutamate, muscarinic acetylcholine and GABA A Speci®c neurochemical changes have been shown to occur in a number of neurotransmitter systems after traumatic brain injury (TBI; for reviews see McIntosh 1994Raghupathi and McIntosh 1998). Positron emission tomography (PET) is a powerful method allowing in vivo visualization and quanti®cation of important physiological parameters. It has been applied in post-traumatic investigation of haemodynamics and metabolism acutely (Hovda et al. 1995;Yamaki et al. 1996;Bergsneider et al. 1997), or later (Lang®tt et al. 1986Humayun et al. 1989;Worley et al. 1995), after traumatic head-injury in humans. However, it has not been applied for identifying often widespread abnormalities in neurotransmission that appear secondary to TBI. Previously, a TBI-induced decrease in Address correspondence and reprint requests to Mats Bergstro Èm, Uppsala University PET Centre, University Hospital, 75185, Uppsala, Sweden. E-mail: mats.bergstrom@pet.uu.seAbbreviations used: B max , maximum speci®c binding; BP, binding potential; FPI,¯uid percussion injury; GABA A -R, gamma-aminobutyric acid A receptor; mACh-R, muscarinic acetylcholine receptor; NMDA-R, N-methyl-d-aspartic acid subtype glutamate receptor; 4-NMPB, 4-Nmethylpiperidylbenzilate; K D , equilibrium dissociation constant; PET, positron emission tomography; TBI, traumatic brain injury.
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