Regional Cerebral Blood Flow After Cortical Impact Injury Complicated by a Secondary Insult in Rats

Abstract

Background and Purpose-Traumatic injury makes the brain susceptible to secondary insults. An uncomplicated mild lateral cortical impact injury (3 m/s, 2.5-mm deformation) that causes little or no permanent sequelae results in a large contusion at the impact site when the traumatic injury is complicated by a secondary insult, such as 40 minutes of bilateral carotid occlusion. Methods-To determine whether the increased sensitivity to secondary insults in this model is caused by a vascular mechanism, cerebral blood flow (CBF) was measured with 14 C-isopropyliodoamphetamine quantitative autoradiography, and brain tissue PO 2 (PbtO 2 ) was measured at the impact site and in the contralateral parietal cortex. Results-In animals that underwent bilateral carotid occlusion 1 hour after the impact injury, CBF and PbtO 2 were lower at the impact site than they were in animals that had either the impact injury or the carotid occlusion alone. In the immediate area of the impact, CBF was 14Ϯ6 mL ⅐ 100 g Ϫ1 ⅐ min Ϫ1 in the animals with the impact injury followed by carotid occlusion compared with 53Ϯ24 mL ⅐ 100 g Ϫ1 ⅐ min Ϫ1 in the animals with the impact injury alone and 74Ϯ14 mL ⅐ 100 g Ϫ1 ⅐ min Ϫ1 in the animals with the carotid occlusion alone (PϽ0.001). At the time of this very low CBF value in the animals with the carotid occlusion after the impact injury, PbtO 2 at the impact site averaged 1.3Ϯ1.6 mm Hg and was Ͻ3 mm Hg in 5 of the 6 animals. In contrast, PbtO 2 in the animals with the impact injury alone averaged 9.3Ϯ2.9 mm Hg, and none of the animals had a PbtO 2 of Ͻ3 mm Hg (Pϭ0.008). Conclusions-The CBF and PbtO 2 findings in this model suggest that the reduced CBF after traumatic injury predisposes the brain to secondary insults and results in ischemia when confronted with a reduction in cerebral perfusion pressure.

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

“…In contrast, other studies in head injured patients have demonstrated histopathological changes consistent with hypoxic/ischemic insults (Graham and Adams, 1971;von Oettingen et al, 2002) and severe flow reductions early after TBI (Bouma et al, 1991;Marion et al, 1991;von Oettingen et al, 2002). Following TBI, energy demand and tissue PO 2 in the traumatized tissue are reduced and, therefore, moderate reductions in blood flow may have severe consequences for cellular survival (Giri et al, 2000). Experimental studies have reported reduction in ATP content in traumatized cortical regions and elevated lactate levels after severe TBI (Lee et al, 1999).…”

Caffeic Acid Phenethyl Ester Protects Blood–Brain Barrier Integrity and Reduces Contusion Volume in Rodent Models of Traumatic Brain Injury

“…The primary event is brief and triggers secondary processes, many of which remain active for hours to days, and contribute to a number of brain pathologies, including neurovascular dysfunction, tissue loss, and neurocognitive impairments (Floyd and Lyeth, 2007;Giri et al, 2000;Hicks et al, 2010;Meaney and Smith, 2011;Ray et al, 2002;Smith et al, 2010;Stoica and Faden, 2010;Werner and Engelhard, 2007;Yakovlev and Faden, 2001). A number of molecular mechanisms that underlie these secondary processes have been identified in rodent models and clinical studies, and represent potential targets for therapeutic intervention (Beauchamp et al, 2008;Fedor et al, 2010;Hayes et al, 2009;Huh and Raghupathi, 2009;Ottens et al, 2010;Saatman et al, 2010;Shellington et al, 2011;Sullivan et al, 2011).…”

Resuscitation of Traumatic Brain Injury and Hemorrhagic Shock with Polynitroxylated Albumin, Hextend, Hypertonic Saline, and Lactated Ringer's: Effects on Acute Hemodynamics, Survival, and Neuronal Death in Mice

“…These observations have been confirmed in experimental studies, in which secondary insults also worsened brain injury. Controlled cortical impact (CCI) with superimposed ischemia reduced cerebral blood flow (CBF) (Giri et al, 2000) and increased hippocampal neuronal loss (Cherian et al, 1996) versus ischemia alone. Jenkins and colleagues (1989) noted increased CA1 neuronal death by combining hemorrhagic hypotension with TBI in rats, and Matsushita and co-workers (2001) reported an increase in contusion area by hemorrhagic shock after fluid percussion injury in rats.…”