Severe Controlled Cortical Impact in Rats: Assessment of Cerebral Edema, Blood Flow, and Contusion Volume

Abstract

Controlled cortical impact (CCI) is a contemporary model of experimental cerebral contusion. We examined the cerebrovascular and neuropathologic effects of a severe CCI in rats. The utility of magnetic resonance imaging (MRI) for the assessment of contusion volume after severe CCI was also established. Severe CCI (3.0 mm depth, 4 m/sec velocity) to the left (L) parietal cortex was produced in anesthetized (isoflurane/N2O/O2), intubated, and mechanically ventilated male Sprague-Dawley rats (n = 58). Physiologic parameters were controlled. The time course of alterations in edema [L-R% brain water (% BW) in 3-mm coronal sections through injured and contralateral hemispheres, wet-dry weight] was evaluated at 2 h, 24 h, 48 h, and 7 days posttrauma. Local cerebral blood flow (ICBF, measured in 8 structures in each hemisphere by autoradiography) was evaluated at 2 h, 24 h, and 7 days. Contusion volume (measured by histology and image analysis) was assessed at 14 days and measured in 6 rats by both MRI and histology. The survival rate after severe CCI was 96.2%. The L-R difference in % BW increased to 1.69 +/- 0.18% at 2 h, 3.00 +/- 0.08% at 24 h, 2.69 +/- 0.09% at 48 h, and 0.94 +/- 0.21% at 7 days. These values all differed from the control (p < 0.05). The % BW was greater at 24 h and 48 h than at 2 h and 7 days (p < 0.05). Marked reductions in ICBF were limited to structures in the injured hemisphere and were observed in the parietal cortex (2 and 24 h), subcortical white matter (2 and 24 h), and hippocampus (2 h), (p < 0.05) vs control rats. In the contusion core, ICBF was 19.4 +/- 8.8 mL 100 g-1 min-1 at 24 h (p = 0.011 vs normal). Necrosis was seen in large portions of the parietal cortex and subcortical white matter, and portions of the hippocampus and thalamus. Contusion volume was 47.8 +/- 9.2 mm3, which represented 14.4 +/- 2.1% of the traumatized hemisphere. Estimates of contusion volume by MRI and histology were closely correlated (r = 0.941, p < 0.017). Severe CCI in rats is accompanied by contusion, reproducible edema, and marked hypoperfusion, involving over 14% of the injured hemisphere, and can be produced with minimal mortality. T2-weighted MRI successfully and noninvasively identifies contusion volume in this model.

Relationship between Flow-Metabolism Uncoupling and Evolving Axonal Injury after Experimental Traumatic Brain Injury

“…The lumped constant has been shown to increase significantly after focal ischemia because of depletion of tissue glucose (Nakai et al, 1987). However, as described in our results and other studies, the CBF reduction associated with experimental trauma is generally above the ischemic threshold except in the contusion core (Yamakami and McIntosh, 1991;Bryan et al, 1995;Kochanek et al, 1995;Forbes et al, 1997;Ginsberg et al, 1997;Richards et al, 2001). Finally it should be noted that we have not attempted to control for any effect of differential exposure to anesthetic between the groups (3 hours exposure versus a brief exposure in the 3-hour and 24-hour injury groups, respectively).…”

“…Disturbances in cerebral blood flow (CBF are also a common sequela of head injury and have been documented both experimentally (Yamakami and McIntosh, 1991;Bryan et al, 1995;Kochanek et al, 1995;Forbes et al, 1997;Hendrich et al, 1999;Lythgoe et al, 2003) and clinically (Bouma et al, 1991;Marion et al, 1991;Martin et al, 1997;Coles et al, 2002). CBF abnormalities have been shown to be an important mechanism underlying secondary brain damage experimentally (Jenkins et al, 1989;Giri et al, 2000) and clinically have been shown to be strongly associated with poor outcome (Robertson et al, 1992).…”

Characterization of the Effects of Adenosine Receptor Agonists on Cerebral Blood Flow in Uninjured and Traumatically Injured Rat Brain using Continuous Arterial Spin-Labeled Magnetic Resonance Imaging

“…Multivariate analysis also revealed an effect of time after injury on CBF. Most investigators have reported an initial reduction in CBF, followed by progressive recovery after experimental TBI (Yamakami and McIntosh, 1989;Kochanek et al, 1995). In saline-treated rats in this study, after severe CCI, CBF recovered by B5% to 50% between B3.5 and B5 h in ROIs beneath the impact site.…”

Prolonged Cyclooxygenase-2 Induction in Neurons and Glia Following Traumatic Brain Injury in the Rat

“…In animal models of TBI, brain prostaglandin levels have been shown to rise rapidly postinjury (Ellis et al, 1989;Dewitt et al, 1988;Shohami et al, 1987). Prostaglandin changes in these studies seemed to be associated with brain injury itself; changes in cerebral blood flow following TBI rarely declined to levels associated with ischemia-induced prostaglandin increases (Obrist et al, 1984;Povlishock and Kontos, 1985;Kempski et al, 1987;Ellis et al, 1988;McIntosh, 1989, 1991;Bouma and Muizelaar, 1992;Muir et al, 1992;Kochanek et al, 1995;von Stück et al, 1996).…”