Regional brain metabolite levels following mild experimental head injury in the cat

Abstract

Glucose, adenosine triphosphate, phosphocreatine, and lactate levels in the cortex, striatum, diencephalon, hippocampus, cerebellum, and brain stem were measured in cats 1 hour after they were subjected to low-level (2 atm) fluid-percussion injury. Following injury, there was a mild but significant increase in lactate levels in the majority of regions studied. The hippocampus exhibited the highest percentage increase in lactate (fourfold). The cortical area directly under the trauma device showed a threefold lactate increase, while there was a twofold increase in other brain regions studied. Although there were consistent decreases in phosphocreatine levels, these decreases were significant only in the hippocampus (p less than 0.05). Glucose levels in all brain regions studied were no different from control levels at the time of study. The unchanged glucose levels, together with previous studies of identically injured cats showing that cerebral blood flow was unimpaired, suggest that excess lactate was not a consequence of cerebral ischemia. Rather, the increase in lactate levels may indicate that concussive injury can produce a mild derangement of brain energy metabolism in the absence of substrate limitations. This derangement may reflect altered mitochondrial function.

Structural and Functional Damage Sustained by Mitochondria after Traumatic Brain Injury in the Rat: Evidence for Differentially Sensitive Populations in the Cortex and Hippocampus

“…Damage or elimination of mitochondrial populations after injury may underlie the sustained hypometabolic state reported to be initiated within hours after experimental TBI (Vink et al, 1988;Yoshino et al, 1991;Ginsberg et al, 1997;Moore et al, 2000) that is coupled to increased brain lactate concentration (Nilsson et al, 1990;Kawamata et al, 1995) and reduced cerebral blood flow (Yamakami and McIntosh, 1991;Ginsberg et al, 1997), suggesting that cerebral metabolism may shift towards anaerobic glycolysis. The acute decrease in the [ATP]/[ADP][P i ] ratio that arises from increases in cytosolic ADP (Vink et al, 1988;Headrick et al, 1994) and reductions in tissue ATP concentrations (Signoretti et al, 2001) (Table 1) incorporates both a loss of energy production and an increase in energy demand after moderate, but not mild (Yang et al, 1985), brain injury. Cerebral metabolic alterations and mitochondrial damage may contribute to the progressive cell death observed in the parietotemporal cortex and CA3 region of the hippocampus after FP brain injury (Hicks et al, 1996;Smith et al, 1997) that would be accompanied by additional loss of mitochondria.…”

Early Microstructural and Metabolic Changes following Controlled Cortical Impact Injury in Rat: A Magnetic Resonance Imaging and Spectroscopy Study

“…Although, most of the TBI rats did not show significantly elevated Lac levels, one out of the eight rats exhibited a dramatic increase of Lac, coupled with a more severe drop in NAA and Glu although the conventional MRI showed similar levels of injury as that of other rats. While the discrepancy in this one rat is unclear, the presence of Lac has been related to multiple factors, including the increased energy demand to restore the ionic balance (Kawamata et al, 1995) and the disordered mitochondrial dysfunction (Ishige et al, 1988;Unterberg et al, 1988;Yang et al, 1985) at the initial stage of the injury. Future studies with histological verification will need to be performed in order to understand the subtle changes that may be responsible for the ischemic conditions far from the injury, as evidenced from increased lactate from the hippocampus and the thalamic region.…”

“…The biochemical and cellular changes in neurons and glia after TBI are complex and dynamic. The pathophysiology typically begins with mechanical trauma to the brain (the primary injury), followed rapidly by increased vascular permeability, altered ionic balance, oxidative stress, excitotoxic damage, inflammation, and mitochondrial dysfunction leading to further cell death and injury (secondary injury) (Hovda et al, 1991;Ishige et al, 1988;Kawamata et al, 1995;Lenzlinger et al, 2001;Morganti-Kossmann et al, 2002;Roberson et al, 2006Xiong et al, 1997Yang et al, 1985).…”

Critical appraisal of neuroprotection trials in head injury: What have we learned?

“…26,27 In the late 70s and 80s, electron microscopy studies confirmed that mitochondrial swelling was an integral part of the subcellular changes following brain injury, 28 and regional brain metabolite level alterations supported mitochondrial dysfunction in TBI. 29 Since then it became progressively clear that disruption of mitochondrial function might play a central role in the pathophysiology of secondary TBI. Mitochondria may act as Ca 2ϩ sinks that sequester Ca 2ϩ to preserve low cytoplasmic Ca 2ϩ concentrations.…”