Effect of Traumatic Brain Injury and Nitrone Radical Scavengers on Relative Changes in Regional Cerebral Blood Flow and Glucose Uptake in Rats

Abstract

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.

Energy Metabolic Changes in the Early Post-injury Period Following Traumatic Brain Injury in Rats

“…Instead, the total adenylate pool is decreased, leading to a reduced capacity for ATP production despite a restoration of the EC in the injured cortical tissue. This mechanism may account for a part of the prolonged energy metabolic depression observed following TBI [15,16].…”

“…It is well established that a TBI results in an increased energy demand due to a disturbance of ion homeostasis [6][7][8][9][10], disturbed glutamatergic neurotransmission [6,[11][12][13] and activation of energy-consuming repair processes [14]. This is reflected by an increased glucose utilisation in the immediate post-injury phase observed in both experimental and clinical TBI [15][16][17][18]. In addition, seizure activity [19][20][21], release of ATP from presynaptic terminals [22], and mitochondrial dysfunction [23][24][25] in combination with a decreased cerebral blood flow post-injury [23-25] may contribute to a disturbed balance between energy demand and supply.…”

Improving Cerebral Blood Flow Through Liposomal Delivery of Angiogenic Peptides: Potential of 18F-FDG PET Imaging in Ischemic Stroke Treatment

“…Brain disorders are often associated with changes in regional cerebral blood flow and glucose metabolism (20,22,23). Despite this, 18 F-FDG PET imaging has limited use, particularly in a clinical setting of cerebral ischemia.…”

Mild Traumatic Brain Injury Results in Depressed Cerebral Glucose Uptake: An 18FDG PET Study

“…For example, immediately after a moderate to severe lateral fluid percussion (LFP) or open or closed skull impact injury in rats, adenosine triphosphate (ATP) levels, N-acetylaspartate (NAA)/ creatinine balance, and CBF decrease, and local cerebral metabolic rate of glucose (lCMRGlc) utilization increases. [11][12][13][14][15][16][17] This apparent uncoupling between metabolism and CBF is short lived, lasting only *6 h in rats. After this time, a metabolic depression sets in with a minimum at 1-2 days post-TBI.…”