Diffusion tensor imaging (DTI) may have prognostic utility in patients with traumatic brain injury (TBI), but the optimal timing of DTI data acquisition is unknown because of dynamic changes in white matter water diffusion during the acute and subacute stages of TBI. We aimed to characterize the direction and magnitude of early longitudinal changes in white matter fractional anisotropy (FA) and to determine whether acute or subacute FA values correlate more reliably with functional outcomes after TBI. From a prospective TBI outcomes database, 11 patients who underwent acute (≤7 days) and subacute (8 days to rehabilitation discharge) DTI were retrospectively analyzed. Longitudinal changes in FA were measured in 11 white matter regions susceptible to traumatic axonal injury. Correlations were assessed between acute FA, subacute FA and the disability rating scale (DRS) score, which was ascertained at discharge from inpatient rehabilitation. FA declined from the acute-to-subacute period in the genu of the corpus callosum (0.70 ± 0.02 vs. 0.55 ± 0.11, p < 0.05) and inferior longitudinal fasciculus (0.54+/−0.07 vs. 0.49+/−0.07, p < 0.01). Acute correlations between FA and DRS score were variable: higher FA in the body (R = −0.78, p = 0.02) and splenium (R = −0.83, p = 0.003) of the corpus callosum was associated with better outcomes (i.e. lower DRS scores), whereas higher FA in the genu of the corpus callosum (R = 0.83, p = 0.02) corresponded with worse outcomes (i.e. higher DRS scores). In contrast, in the subacute period higher FA in the splenium correlated with better outcomes (R = −0.63, p < 0.05) and no inverse correlations were observed. White matter FA declined during the acute-to-subacute stages of TBI. Variability in acute FA correlations with outcome suggests that the optimal timing of DTI for TBI prognostication may be in the subacute period.

Neuroinflammation plays a crucial role in traumatic brain injury (TBI), contributing to both damage and recovery, yet no effective therapy exists to mitigate central nervous system (CNS) injury and promote recovery after TBI. In the present study, we found that nasal administration of an anti-CD3 monoclonal antibody ameliorated CNS damage and behavioral deficits in a mouse model of contusional TBI. Nasal anti-CD3 induced a population of interleukin (IL)-10-producing regulatory T cells (T_reg cells) that migrated to the brain and closely contacted microglia. T_reg cells directly reduced chronic microglia inflammation and regulated their phagocytic function in an IL-10-dependent manner. Blocking the IL-10 receptor globally or specifically on microglia in vivo abrogated the beneficial effects of nasal anti-CD3. However, the adoptive transfer of IL-10-producing T_reg cells to TBI-injured mice restored these beneficial effects by enhancing microglial phagocytic capacity and reducing microglia-induced neuroinflammation. These findings suggest that nasal anti-CD3 represents a promising new therapeutic approach for treating TBI and potentially other forms of acute brain injury.

There has been improvement in the care of patients with traumatic spinal cord injuries, particularly in the prehospital evaluation, approach for immediate immobilization, standardized spinal clearance, efficient triage, and transportation of appropriate patients to traumatic spinal cord injury specialized centers. Advancements in spinal instrumentation have improved the surgical management of spinal fractures and the ability to manage patients with spinal mechanical instability. The clinical evidence favors performing early surgical decompression and spine stabilization within 24 hours of traumatic spinal cord injuries, regardless of the severity or location of the injury. There is no evidence that supports the use of neuroprotective treatments to improve outcomes in patients with traumatic spinal cord injuries. The administration of high-dose methylprednisolone, which is associated with significant systemic adverse effects, is strongly discouraged. Early and delayed mortality rates continue to be high in patients with traumatic spinal cord injuries, and survivors often confront substantial long-term physical and functional impairments. Whereas the exploration of neuroregenerative approaches, such as stem cell transplantation, is underway, these methods remain largely investigational. Further research is still necessary to advance the functional recovery of patients with traumatic spinal cord injuries. ESSENTIAL POINTS Traumatic spinal cord injury is a complex and devastating condition that leads to long-term neurologic deficits with profound physical, social, and vocational implications, resulting in a diminished quality of life, particularly for severely affected patients. The initial management of traumatic spinal cord injuries demands comprehensive interdisciplinary care to address the potentially catastrophic multisystem effects. Ongoing endeavors are focused on optimizing and customizing initial management approaches and developing effective therapies for neuroprotection and neuroregeneration to enhance long-term functional recovery....

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality. The innate and adaptive immune responses play an important role in the pathogenesis of TBI. Gamma-delta (γδ) T cells have been shown to affect brain immunopathology in multiple different conditions, however, their role in acute and chronic TBI is largely unknown. Here, we show that γδ T cells affect the pathophysiology of TBI as early as one day and up to one year following injury in a mouse model. TCRδ^−/− mice are characterized by reduced inflammation in acute TBI and improved neurocognitive functions in chronic TBI. We find that the Vγ1 and Vγ4 γδ T cell subsets play opposing roles in TBI. Vγ4 γδ T cells infiltrate the brain and secrete IFN-γ and IL-17 that activate microglia and induce neuroinflammation. Vγ1 γδ T cells, however, secrete TGF-β that maintains microglial homeostasis and dampens TBI upon infiltrating the brain. These findings provide new insights on the role of different γδ T cell subsets after brain injury and lay down the principles for the development of targeted γδ T-cell-based therapy for TBI.