The Frontal Lobe and Thalamus Have Different Sensitivities to Hypoxia-Hypotension after Traumatic Brain Injury: A Microdialysis Study in Rats

Abstract

After traumatic brain injury (TBI), lesions are anatomically heterogeneous, but the spatial heterogeneity of the post-traumatic brain's vulnerability to hypoxia-hypotension (HH) has been poorly studied. Our objective was to compare the effect of HH after TBI on brain energy metabolism into two regions: the frontal lobe and the thalamus. Twenty-eight Sprague-Dawley rats were randomized into four groups: sham, TBI (brain trauma alone, impact acceleration, 450-g weight drop from 1.8 m), HH (blood depletion to mean arterial pressure 40 mm Hg, FiO(2) 10%, 15 min), and TBI-HH (TBI followed by HH, 45-min delay). Cerebral perfusion pressure (CPP) was continuously measured. Brain microdialysis and brain tissue oxygen partial pressure (PtiO(2)) probes were both inserted stereotaxically into the right thalamus and frontal lobe. Except during the HH period, CPP was always above 60 mm Hg. During the hour following the HH period, significant increases in cerebral lactate-pyruvate ratio, glycerol, and glutamate were observed, and were always higher in the frontal lobe than in the thalamus (p<0.001). In the TBI-HH group and in the frontal lobe, increases in glutamate and glycerol were significantly higher than in the HH group (p<0.001). During the 30 min following the HH phase (reperfusion), an increase in PtiO(2) was observed. In the TBI-HH group, this increase was significantly lower in the frontal lobe than in the thalamus. These findings demonstrate that in the early post-traumatic period, the metabolic cerebral response to HH is higher in the frontal lobe than in the thalamus, and is worsened by TBI, suggesting a higher vulnerability for the frontal lobes.

Cerebral and extracerebral vulnerability to hypoxic insults after diffuse traumatic brain injury in rats

“…Less changes in edema, ADC and cerebral metabolism have been described following TBI in the thalamus compared to the cortex (Blanie et al, 2012;Ito et al, 1996;Kita and Marmarou, 1994). Ito et al (1996) using the same model than ours (impactacceleration model in rats) found at 2 h, a 17% decrease in ADC in the thalamus vs. a 44% decrease in ADC in the cortex for rats with TBI and HH.…”

“…Moreover, posttraumatic insult was less aggressive, as only hypoxia was used. Indeed, the combination of hypoxia and hypotension is necessary to obtain edema formation, raise in ICP or changes in cerebral metabolites in this rat model of TBI with secondary insults (Blanie et al, 2012;Gabrielian et al, 2011;Geeraerts et al, 2006Geeraerts et al, , 2008. Recently, Blanié et al (2012) compared the effect of HH after TBI on brain energy metabolism in the frontal lobe and in the thalamus.…”

“…A short delay (30 min) between TBI and HH was therefore used in the present study. This rat model had been used and validated to describe cerebral consequences of associated injuries in standardized conditions (Blanie et al, 2012;Geeraerts et al, 2006Geeraerts et al, , 2008.…”

“…The thalamus and striatum appear to be less vulnerable than cortex and hippocampus in literature (Blanie et al, 2012;Ito et al, 1996). Less changes in edema, ADC and cerebral metabolism have been described following TBI in the thalamus compared to the cortex (Blanie et al, 2012;Ito et al, 1996;Kita and Marmarou, 1994).…”

Where are we in the modelling of traumatic brain injury? Models complicated by secondary brain insults

“…They further observed that the combined effects on brain energy metabolism were not related to modifications in cerebral perfusion pressure (CPP) or CBF. Most recently, the spatial heterogeneity of the posttraumatic brain's vulnerability to hypotension-hypoxemia is described using the 'more-hit' combined model [102]. The combined effect of hypotensive-hypoxemia has been definitively demonstrated; however, the combination of other secondary insults is rarely incorporated into the models of TBI and the associated effects on the injured brain are seldom recognized.…”