Translational approach towards determining the role of cerebral autoregulation in outcome after traumatic brain injury

Abstract

Cerebral autoregulation is impaired after traumatic brain injury (TBI), contributing to poor outcome. In the context of the neurovascular unit, cerebral autoregulation contributes to neuronal cell integrity and clinically Glasgow Coma Scale is correlated to intactness of autoregulation after TBI. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP) and thereby limit impairment of cerebral autoregulation and neurological deficits. However, current vasoactive agent choice used to elevate MAP to increase CPP after TBI is variable. Vasoactive agents, such as phenylephrine, dopamine, norepinephrine, and epinephrine, clinically have not sufficiently been compared regarding effect on CPP, autoregulation, and survival after TBI. The cerebral effects of these clinically commonly used vasoactive agents are incompletely understood. This review will describe translational studies using a more human like animal model (the pig) of TBI to identify better therapeutic strategies to improve outcome post injury. These studies also investigated the role of age and sex in outcome and mechanism(s) involved in improvement of outcome in the setting of TBI. Additionally, this review considers use of inhaled nitric oxide as a novel neuroprotective strategy in treatment of TBI.

Neuroprotective Effect of Low-Intensity Transcranial Ultrasound Stimulation in Moderate Traumatic Brain Injury Rats

“…For example, cerebral microcirculation disturbance can aggravate ischemia and hypoxia, decrease ATP synthesis, and destroy blood-brain barrier. In addition, the increase in monoamine neurotransmitters, glutamic acid, nitric oxide, bradykinin, endothelin, and arachidonic acid also participate in the occurrence and development of traumatic brain edema (Li et al, 2015;Kozlov et al, 2017;Treble-Barna et al, 2017;Armstead and Vavilala, 2019;Morris et al, 2019). No matter what the pathogenesis of TBI are, the brain tissue edema and nerve fiber damage will occur, which will cause the FA value to decrease and the MD value to increase in DTI (Hanks et al, 2019).…”

A Narrative Review on Translational Research in Acute Brain Injury

“…13 Although early data suggest that dopamine should be considered as a first-line treatment to protect AR and improve outcomes, still further basic research is required to see the associated capillary blood flow changes and neurotoxic changes. 12 The choice between mannitol or hypertonic saline for reducing ICP still eludes us. Both these agents are considered to modulate polymorphonuclear neutrophil (PMN) and endothelial cell (EC) activation.…”

“…11 The cerebral effect of vasoactive drugs on the preclinical model of TBI has shown that the choice of drug affects AR and CPP. 12 The elevation of mean arterial pressure (MAP) to improve CPP after TBI is insufficient alone to improve outcomes, and maintenance of AR is also an important factor in determining the final outcome. 13 Although early data suggest that dopamine should be considered as a first-line treatment to protect AR and improve outcomes, still further basic research is required to see the associated capillary blood flow changes and neurotoxic changes.…”

“…13 Although early data suggest that dopamine should be considered as a first-line treatment to protect AR and improve outcomes, still further basic research is required to see the associated capillary blood flow changes and neurotoxic changes. 12…”

Sex Differences in Mitochondrial Function Following a Controlled Cortical Impact Traumatic Brain Injury in Rodents

“…Cerebral autoregulation maintains normal cerebral blood flow(CBF) across a range of blood pressures to ensure sufficient oxygen and glucose can get to their destinations. Cerebral autoregulation is impaired after TBI causing CBF to decrease, which often leads to poor patient outcomes making this one of the important targets for therapeutic intervention following TBI (Roof and Hall, 2000 ; Jalloh et al, 2015 ; Armstead and Vavilala, 2019 ). It was found that cerebral glucose utilization in some brain regions, including the hippocampus, varied with the phases of the estrus cycle in uninjured, normal cycling female rats compared to male rats (Nehlig et al, 1985 ).…”