Hippocampal CA₃Lesion Prevents Postconcussive Metabolic Dysfunction in CA₁

Abstract

Summary: Immediately following fluid-percussion (F-P) brain injury, the hippocampus exhibits a marked increase in its local CMR g lc (LCMR g l c ; ILmol/lOO g/min) as deter mined using [14C]2-deoxY-D-glucose autoradiography. This injury-induced increase in metabolism is followed in 6 h by a subsequent decrease in LCMR g lc' These two postinjury metabolic states may be the result of ionic dis ruptions following trauma via stimulation of glutamate gated ion channels. To determine if endogenous gluta mate innervation to the CAl region of the hippocampus can provide an anatomical basis for this proposed mech anism, it was removed by kainic-acid-induced destruc tion of CA3, and the effect on CAl metabolism following concussive injury was studied. Five days before a lateral F-P injury (3.5-4.5 atm), kainic acid (0.5 ILg) or vehicle was stereotaxically injected into the left ventricle of 65 rats. Histological inspection indicated that kainic acid produced severe cell loss primarily in the CA3 region of the hippocampus ipsilateral to the injection. The meta bolic results indicated that immediately following injury, animals with an intact hippocampus exhibited an increase Following cerebral concussion in the rat, as pro duced using fluid-percussion (F-P) , the cerebral cortex and hippocampus exhibit pronounced changes in glucose metabolism. During the acute period, these regions exhibit a marked increase in this metabolism as determined by e 4 C]2-deoxY-D-

Local Cerebral Glucose Utilization and Cytoskeletal Proteolysis as Indices of Evolving Focal Ischemic Injury in Core and Penumbra

“…In the hippocampus, in creased glucose utilization was seen in occasional rats. A similar pattern of increased glucose utiliza tion has been observed in the hippocampus of a gerbil model of focal ischemia (Miyashita et al,199 1) and in traumatic cortical injury in the rat (Yoshino et al , 1992). In the latter study, a lesion of area CA3 of hippocampus prevented abnormal postconcussive glucose metabolism in area CAL We assume, therefore, that this type of apparent hippocampal hypermetabolism outside the ischemic focus may be due to activation via neural pathways from cerebral cortex to hippocampus.…”

An NMR metabolomic investigation of early metabolic disturbances following traumatic brain injury in a mammalian model

“…Therefore, we cannot exclude the occurrence of either acute, transient metabolic changes or longer term changes in energy metabolism. Previous studies focusing on brain metabolic studies 24 reported a biphasic metabolic response characterized by rapid hypermetabolism followed by a longer lasting period of hypometabolism. Our observations at 1 h post-TBI may have coincided with a transition from hyper to hypometabolism.…”

Metabolic and Histologic Effects of Sodium Pyruvate Treatment in the Rat after Cortical Contusion Injury

“…TBI-induced glutamate release and ionic fluxes (Faden et al, 1989;Katayama et al, 1990Katayama et al, , 1995Yoshino et al, 1992;Fineman et al, 1993;Palmer et al, 1993;Rose et al, 2002) initiate increased metabolic demands, reflected in early, transient increases in cerebral metabolic rates for glucose (Sunami et al, 1989b;Yoshino et al, 1991;Kawamata et al, 1992;Sutton et al, 1994;Lee et al, 1999) and increased anaerobic glycolysis, reflected by an increase in extracellular and tissue lactate levels Dhillon et al, 1997;Bartnik et al, 2005Bartnik et al, , 2007b. TBI is also known to induce mitochondrial dysfunction (Vink et al, 1990;Verweij et al, 1997;Xiong et al, 1997), increase free radical production and oxidative stress (Hall et al, 1993(Hall et al, , 2004Marklund et al, 2001;Tavazzi et al, 2005), induce zinc release and accumulation (Suh et al, 2000(Suh et al, , 2006Hellmich et al, 2004Hellmich et al, , 2007, and activate poly(ADP-ribose) polymerases (PARP) (Laplaca et al, 1999;Besson et al, 2003;Satchell et al, 2003;Clark et al, 2007).…”