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Traumatic brain injury (TBI) results from direct penetrating and indirect non-penetrating forces that alters brain functions, affecting millions of individuals annually. Primary injury following TBI is exacerbated by secondary brain injury; foremost is the deleterious inflammatory response. One therapeutic intervention being increasingly explored for TBI is hyperbaric oxygen therapy (HBOT), which is already approved clinically for treating open wounds. HBOT consists of 100% oxygen administration, usually between 1.5 and 3 atm and has been found to increase brain oxygenation levels after hypoxia in addition to decreasing levels of inflammation, apoptosis, intracranial pressure, and edema, reducing subsequent secondary injury. The following review examines recent preclinical and clinical studies on HBOT in the context of TBI with a focus on contributing mechanisms and clinical potential. Several preclinical studies have identified pathways, such as TLR4/NF-kB, that are affected by HBOT and contribute to its therapeutic effect. Thus far, the mechanisms mediating HBOT treatment have yet to be fully elucidated and are of interest to researchers. Nonetheless, multiple clinical studies presented in this review have examined the safety of HBOT and demonstrated the improved neurological function of TBI patients after HBOT, deeming it a promising avenue for treatment.

Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting. Separately, fibrinogen split products induce fibrinogen production, thereby elevating plasma fibrinogen levels. Thus, the hypothesis was that preconditioning with C. atrox venom will produce fibrinogen spilt products, thereby upregulating fibrinogen levels, ultimately improving perioperative hemostasis during SBI. We observed that Cv-PC SBI animals had significantly reduced intraoperative hemorrhage and postoperative hematoma volumes compared to those of vehicle preconditioned SBI animals. Cv-PC animals were also found to have higher levels of plasma fibrinogen at the time of surgery, with unchanged prothrombin time. Cv-PC studies with fractions of C. atrox venom suggest that snake venom metalloproteinases are largely responsible for the improved hemostasis by Cv-PC. Our findings indicate that Cv-PC increases plasma fibrinogen levels and may provide a promising therapy for reducing perioperative hemorrhage in elective surgeries.

The classical neurovascular unit (NVU), composed primarily of endothelium, astrocytes, and neurons, could be expanded to include smooth muscle and perivascular nerves present in both the up- and downstream feeding blood vessels (arteries and veins). The extended NVU, which can be defined as the vascular neural network (VNN), may represent a new physiological unit to consider for therapeutic development in stroke, traumatic brain injury, and other brain disorders (Zhang et al., Nat Rev Neurol 8(12):711-716, 2012). This review is focused on traumatic brain injury and resultant post-traumatic changes in cerebral blood flow, smooth muscle cells, matrix, blood-brain barrier structures and function, and the association of these changes with cognitive outcomes as described in clinical and experimental reports. We suggest that studies characterizing TBI outcomes should increase their focus on changes to the VNN, as this may yield meaningful therapeutic targets to resolve posttraumatic dysfunction.

Objective: We evaluated proton magnetic resonance spectroscopic imaging (MRSI) findings for children with traumatic brain injury attributable to nonaccidental trauma (NAT) early after injury, to determine whether brain metabolite changes predicted outcomes., Methods: Proton MRSI (1.5 T) was performed (mean: 5 days after injury [range: 1-30 days]) through the level of the corpus callosum for 90 children with confirmed NAT. Regional N-acetylaspartate/total creatine, N-acetylaspartate/total choline, and choline/creatine ratios and the presence of lactate were measured. Data on long-term outcomes defined at > or =6 months were collected for 44 of 90 infants. We grouped patients into good (normal, mild disability, or moderate disability; n = 32) and poor (severe disability, vegetative state, or dead; n = 12) outcome groups., Results: We found that N-acetylaspartate/creatine and N-acetylaspartate/choline ratios (mean total, corpus callosum, and frontal white matter) were significantly decreased in patients with poor outcomes (P < .001). A logistic regression model using age, initial Glasgow Coma Scale score, presence of retinal hemorrhage, lactate on MRSI scans, and mean total N-acetylaspartate/creatine ratio predicted outcomes accurately in 100% of cases., Conclusions: Reduced N-acetylaspartate levels (ie, neuronal loss/dysfunction) and elevated lactate levels (altered energy metabolism) correlated with poor neurologic outcomes for infants with NAT. Elevated lactate levels may reflect primary or secondary hypoxic-ischemic injury, which may occur with NAT. Our data suggest that MRSI performed early after injury can be used for long-term prognosis.