In November 2017, the Lancet Neurology Commission on Traumatic Brain Injury (TBI) highlighted existing deficiencies in epidemiology, patient characterization, identifying best practice, outcome assessment, and evidence generation. The Commission concluded that C needed to address deficiencies in prevention , and made a recommendation for large collaborative studies which could provide the framework for precision medicine and comparative effectiveness research (CER).

Summary: These experiments examined the effects of moderate hypothermia on mortality and neurological def icits observed after experimental traumatic brain injury (TBI) in the rat. Brain temperature was measured contin uously in all experiments by intraparenchymal probes, Brain cooling was induced by partial immersion (skin pro tected by a plastic barrier) in a water bath (OOe) under general anesthesia (1.5% halothane170% nitrous oxide/ 30% oxygen). In experiment I, we examined the effects of moderate hypothermia induced prior to injury on mortal ity following fluid percussion TBI. Rats were cooled to 36°e (n = 16), 33°e (n = 17), or 300e (n = II) prior to injury and maintained at their target temperature for I h after injury. There was a significant (p < 0.04) reduction in mortality by a brain temperature of 30oe. The mortality rate at 36°e was 37.5%, at 33°e was 41 %, and at 300e wasThe cerebral protective effects of profound hypo thermia «18°C) have been known for many years. As early as 1950, reports of cerebral protection from global ischemia by profound hypothermia in animals stimulated clinical interest (Mohri and Me rendino, 1969). By 1955, 100 cardiac surgical cases had been performed under deep hypothermia with cardiac arrest (Mohri and Merendino, 1969). As pump oxygenators became more efficient, deep hy pothermia and cardiac arrest were only occasion ally used in adult cardiac surgery (Crawford and Saleh, 1981). In pediatric cardiac surgery, however, conditions were encountered routinely where total cessation of circulation at temperatures of 17-20°C Abbreviations used: ANOYA, analysis of variance; TB1, trau matic brain injury, 114 9.1 %. In experiment II, we examined the effects of mod erate hypothermia or hyperthermia initiated after TBI 01 long-term behavioral deficits. Rats were cooled to 36°e (I = 10), 33°e (n = 10), or 300e (n = 10) or warmed to 38°( (n = 10) or 400e (n = 12) starting at 5 min after injury an( maintained at their target temperatures for I h. Hypother mia-treated rats had significantly less beam-walking beam-balance, and body weight loss deficits compared t( normothermic (38°C) rats. The greatest protection wa: observed in the 300e hypothermia group, Since a temper ature of 300e can be induced in humans by surface cool ing without coagulopathy or ventricular fibrillation, hy pothermia to 300e may have potential clinical value fOJ treatment of human brain injury.

Small direct current (DC) electric fields (EFs) guide neurite growth and migration of rodent neural stem cells (NSCs). However, this could be species dependent. Therefore, it is critical to investigate how human NSCs (hNSCs) respond to EF before any possible clinical attempt. Aiming to characterize the EF-stimulated and guided migration of hNSCs, we derived hNSCs from a well-established human embryonic stem cell line H9. Small applied DC EFs, as low as 16 mV/mm, induced significant directional migration toward the cathode. Reversal of the field polarity reversed migration of hNSCs. The galvanotactic/electrotactic response was both time and voltage dependent. The migration directedness and distance to the cathode increased with the increase of field strength. (Rho-kinase) inhibitor Y27632 is used to enhance viability of stem cells and has previously been reported to inhibit EF-guided directional migration in induced pluripotent stem cells and neurons. However, its presence did not significantly affect the directionality of hNSC migration in an EF. Cytokine receptor [C-X-C chemokine receptor type 4 (CXCR4)] is important for chemotaxis of NSCs in the brain. The blockage of CXCR4 did not affect the electrotaxis of hNSCs. We conclude that hNSCs respond to a small EF by directional migration. Applied EFs could potentially be further exploited to guide hNSCs to injured sites in the central nervous system to improve the outcome of various diseases.

To compare the effect of long-term mild hypothermia versus short-term mild hypothermia on the outcome of 215 severe traumatic brain injured patients with cerebral contusion and intracranial hypertension. At three medical centers, 215 patients aged 18 to 45 years old with an admission Glasgow Coma Scale <-8 within 4 h after injury were randomly divided into two groups: long-term mild hypothermia group (n = 108) for 5 +-1.3 days mild hypothermia therapy and short-term mild hypothermia group (n = 107) for 2 +-0.6 days mild hypothermia therapy. All patients had intracranial hypertension and frontotemporoparietal contusion with midline shift > 1 cm confirmed on computed tomographic scan. Glasgow Outcome Scale at 6-month follow-up, 47 cases had favorable outcome (43.5%), and other 61 cases had unfavorable outcome (56.5%) in the long-term mild hypothermia group. However, only 31 cases had favorable outcome (29.0%), and other 76 cases had unfavorable outcome (71.0%) in the short-term mild hypothermia group (P < 0.05). The intracranial pressure significantly rebounded after rewarming in the short-term mild hypothermia group, but not in the long-term mild hypothermia (P < 0.05). Furthermore, the incidence of stress ulcer, epilepsy, pulmonary infection, intracranial infection did not significantly differ between the two groups (P > 0.05). Compared with short-term mild hypothermia, long-term mild hypothermia significantly improves the outcome of severe traumatic brain injured patients with cerebral contusion and intracranial hypertension without significant complications. Our data suggest that 5 days of longterm cooling is more efficacious than 2 days of short-term cooling when mild hypothermia is used to control refractory intracranial hypertension in patients with severe traumatic brain injury.

SummaryLimited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies.