The Acute Effects of Hemorrhagic Shock on Cerebral Blood Flow, Brain Tissue Oxygen Tension, and Spreading Depolarization following Penetrating Ballistic-Like Brain Injury

Abstract

Traumatic brain injury (TBI) often occurs in conjunction with additional trauma, resulting in secondary complications, such as hypotension as a result of blood loss. This study investigated the combined effects of penetrating ballistic-like brain injury (PBBI) and hemorrhagic shock (HS) on physiological parameters, including acute changes in regional cerebral blood flow (rCBF), brain tissue oxygen tension (P(bt)O₂), and cortical spreading depolarizations (CSDs). All recordings were initiated before injury (PBBI/HS/both) and maintained for 2.5 h. Results showed that PBBI alone and combined PBBI and HS produced a sustained impairment of ipsilateral rCBF that decreased by 70% from baseline (p<0.05). Significant and sustained reductions in P(bt)O₂ (50% baseline; p<0.05) were also observed in the injured hemisphere of the animals subjected to both PBBI and HS (PBBI+HS). In contrast, PBBI alone produced smaller, more transient reductions in P(bt)O₂ levels. The lower limit of cerebral autoregulation was significantly higher in the PBBI+HS group (p<0.05, compared to HS alone). Critically, combined injury resulted in twice the number of spontaneous CSDs as in PBBI alone (p<0.05). It also lowered the propagation speed of CSD and the threshold of CSD occurrence [induced CSD at higher mean arterial pressure (MAP)]. However, rCBF and P(bt)O₂ were not responsive to the depolarizations. Our data suggest that PBBI together with HS causes persistent impairment of CBF and brain tissue oxygen tension, increasing the probability of CSDs that likely contribute to secondary neuropathology and compromise neurological recovery.

Outcomes after concomitant traumatic brain injury and hemorrhagic shock

“…22 Combined hypoxemia and hemorrhagic shock in animal models of TBI + HS have been associated with transient intracerebral reductions in brain glucose, pyruvate, and prolonged elevations of lactate. 23,24 Energy-related neurochemical dysregulation in TBI + HS is likely a major factor contributing to worse neurologic outcomes.…”

“…Whereas brain injury has been shown to cause altered vascular compensation in response to HS, 31 questions remain about the relationship between coagulopathy and the size of brain lesions. 15,22,30,32,33 Ratio-guided resuscitation with fresh frozen plasma (FFP) may have beneficial effects for patients with TBI + HS, 15 including fewer inflammatory complications. 5,6,9 In experimental large animal studies, early administration of FFP reduced the size of brain lesions, decreased cerebral edema, and substantially attenuated the degree of neurological impairment.…”

“…Most studies of TBI and HS have been focused on neuronal death, 33 neurochemical changes, 23 or other physiological mechanisms, 22,24 and none have been done in humans. While the number of patients in this post hoc analysis of patients previously randomized in PROPPR yielded a modest number of patients with TBI and HS, to our knowledge, this represents the largest study population with these two conditions conducted to date.…”

Traumatic Brain Injury Pathophysiology and Treatments: Early, Intermediate, and Late Phases Post-Injury

“…As expected, rodents subject to penetrating ballistic-like brain injury (PBBI) display a 70% reduction in regional cerebral blood flow (CBF) ipsilateral to the injury as compared to baseline. PBBI also decreases brain tissue oxygenation tension and causes spreading cortical depolarizations shortly after injury [5]. CBF reductions are more pronounced in older compared to younger rodents, as seen with fluid percussion injury (FPI) TBI [6].…”

Analysis of Cerebral Hemodynamics in Healthy Adult Rhesus with Dynamic Susceptibility Contrast Perfusion (DSC-MR) Imaging

“…It is very sensitive to ischemia and hypoxia. When the cerebral blood flow (CBF) is less than 12-20 ml/ (100 g/min), it will lead to insufficient blood supply to the brain [2], causing microcirculation perfusion, functional disorders of cell membrane Na-K pump, intracellular anaerobic glycolysis, generation of cytotoxic edema, ischemia, bloodbrain barrier damages, and further aggravation of the brain damage. Study has showed microcirculation perfusion abnormalities that appeared before the cytotoxic edema and vasogenic edema [3].…”