Histopathological and Behavioral Effects of Immediate and Delayed Hemorrhagic Shock after Mild Traumatic Brain Injury in Rats

Abstract

The purpose of this study was to investigate the increased susceptibility of the brain, after a controlled mild cortical impact injury, to a secondary ischemic insult. The effects of the duration and the timing of the secondary insult after the initial cortical injury were studied. Rats anesthetized with isoflurane underwent a 3 m/sec, 2.5-mm deformation cortical impact injury followed by hypotension to 40 mm Hg induced by withdrawing blood from a femoral vein. The duration of hypotension was varied from 40 to 60 min. The timing of 60 min of hypotension was varied from immediately post-injury to 7 days after the injury. Outcome was assessed by behavioral tasks and histological examination at 2 weeks post-injury. A separate group of animals underwent measurement of the acute physiology including mean blood pressure (MAP), intracranial pressure (ICP), and cerebral blood flow (CBF) using a laser Doppler technique. Increasing durations of hypotension resulted in marked expansion of the contusion, from 6.5±1.8 mm³ with sham hypotension to 27.1±3.9 mm³ with 60 min of hypotension. This worsening of the contusion was found only when then hypotension occurred immediately after injury or at 1 h after injury. CA3 neuron loss followed a similar pattern, but the injury group differences were not significant. Motor tasks, including beam balance and beam walking, were significantly worse following 50 and 60 min of hypotension. Performance on the Morris water maze task was also significantly related to the injury group. Studies of the acute cerebral hemodynamics demonstrated that CBF was significantly more impaired during hypotension in the animals that underwent the mild TBI compared to those that underwent sham TBI. The perfusion deficit was worst at the impact site, but also significant in the pericontusional brain. With 50 and 60 min of hypotension, CBF did not recover following resuscitation at the impact site, and recovered only transiently in the pericontusional brain. These results demonstrate that mild TBI, like more severe levels of TBI, can impair the brain's ability to maintain CBF during a period of hypotension, and result in a worse outcome.

Early treatment with lyophilized plasma protects the brain in a large animal model of combined traumatic brain injury and hemorrhagic shock

“…2,24 Animal experiments have also demonstrated that longer durations of hypotension result in marked expansion in the brain lesion size. 25 Therefore, appropriate resuscitation is important in patients where TBI is complicated by the presence of HS. 26,27 The role of intravenous fluid therapy in prehospital trauma care is controversial.…”

Inhibition of Eukaryotic Initiation Factor 2 Alpha Phosphatase Reduces Tissue Damage and Improves Learning and Memory after Experimental Traumatic Brain Injury

“…Previous clinical and experimental studies have shown that postinjury hypotension can exacerbate tissue damage. 72,73 For example, a recent study by Robertson and colleagues has reported that a 60-min period of hypotension (MAP reduced to 40 mm Hg), when initiated up to 1 h postinjury, significantly increases cortical contusion volume. 72 Although we have observed that guanabenz can cause a similar reduction in blood pressure in uninjured anesthetized animals (data not shown), both acute (30 min postinjury) and delayed (24 h postinjury) administration of 5.0 mg/kg of guanabenz reduced cortical tissue loss.…”

“…72,73 For example, a recent study by Robertson and colleagues has reported that a 60-min period of hypotension (MAP reduced to 40 mm Hg), when initiated up to 1 h postinjury, significantly increases cortical contusion volume. 72 Although we have observed that guanabenz can cause a similar reduction in blood pressure in uninjured anesthetized animals (data not shown), both acute (30 min postinjury) and delayed (24 h postinjury) administration of 5.0 mg/kg of guanabenz reduced cortical tissue loss. Although the longer delay did not offer significant hippocampal protection, determination of the therapeutic window may help to maximize neuroprotection while minimizing adverse influences associated with postinjury mean arterial pressure (MAP) reduction.…”

Increased Intracranial Pressure after Diffuse Traumatic Brain Injury Exacerbates Neuronal Somatic Membrane Poration but not Axonal Injury: Evidence for Primary Intracranial Pressure-Induced Neuronal Perturbation

“…If at any point during the experiment the CPP or MABP decreased below normal autoregulatory limits (CPP < 50 mm Hg and MABP < 60 mm Hg; (Bratton et al, 2007a (http://www. braintrauma.org/coma-guidelines/); Dennis et al, 2009;Navarro et al, 2012); dashed lines Figures 1B and 1C), then the animal was excluded from analysis. Note that throughout the majority of the experiment the MABP of animals sustaining injury, irrespective of the pattern of postinjury ICP, was comparable to the sham-injured group ( Figure 1B).…”