Journal of neurotrauma
-
Journal of neurotrauma · Aug 2024
Molecular pathway changes associated with different post-conditioning exercise interventions after experimental TBI.
Traumatic brain injury (TBI) causes complex, time-dependent molecular and cellular responses, which include adaptive changes that promote repair and recovery, as well as maladaptive processes such as chronic inflammation that contribute to chronic neurodegeneration and neurological dysfunction. Hormesis is a well-established biological phenomenon in which exposure to low-dose toxins or stressors results in protective responses to subsequent higher-level stressors or insults. Hormetic stimuli show a characteristic U-shaped or inverted J-shaped dose-response curve, as well as being time and exposure-frequency dependent, similar to pre-conditioning and post-conditioning actions. ⋯ Exercise initiated at a more delayed timepoint of 6 weeks after injury and continuing for 4 weeks was more effective than that during the acute phase. The delayed paradigm was also more effective than exercise initiated at 10 weeks after injury and continuing for 8 weeks, consistent with hormetic responses in other models and species. Overall, our study delineates regional and interventional parameters, as well as related molecular pathway changes, associated with post-conditioning exercise treatment, which may help inform future translational interventional strategies.
-
Journal of neurotrauma · Aug 2024
Evidence for Altered White Matter Organisation After Mild Traumatic Brain Injury: A Scoping Review on the Use of Diffusion MRI and Blood-Based Biomarkers to Investigate Acute Pathology and Relationship to Persistent Post-Concussion Symptoms.
Mild traumatic brain injury (mTBI) is the most common form of traumatic brain injury. Post-concussive symptoms typically resolve after a few weeks although up to 20% of people experience these symptoms for >3 months, termed persistent post-concussive symptoms (PPCS). Subtle white matter (WM) microstructural damage is thought to underlie neurological and cognitive deficits experienced post-mTBI. ⋯ Significant biomarker alterations were frequently associated with heightened symptom burden and prolonged recovery time post-injury. These data suggest that dMRI and blood-based biomarkers may be useful proxies of WM organization, although few studies assessed these complementary measures in parallel, and the relationship between modalities remains unclear. Further studies are warranted to assess the benefit of a combined biomarker approach in evaluating alterations to WM organization after mTBI.
-
Journal of neurotrauma · Aug 2024
Hepatocyte growth factor delivery to injured cervical spinal cord using an engineered biomaterial protects respiratory neural circuitry and preserves functional diaphragm innervation.
A major portion of spinal cord injury (SCI) cases occur in the cervical region, where essential components of the respiratory neural circuitry are located. Phrenic motor neurons (PhMNs) housed at cervical spinal cord level C3-C5 directly innervate the diaphragm, and SCI-induced damage to these cells severely impairs respiratory function. In this study, we tested a biomaterial-based approach aimed at preserving this critical phrenic motor circuitry after cervical SCI by locally delivering hepatocyte growth factor (HGF). ⋯ HGF hydrogel also preserved PhMN innervation of the diaphragm, as assessed by both retrograde PhMN tracing and detailed neuromuscular junction morphological analysis. Furthermore, HGF hydrogel significantly decreased lesion size and degeneration of cervical motor neuron cell bodies, as well as reduced levels surrounding the injury site of scar-associated chondroitin sulfate proteoglycan molecules that limit axon growth capacity. Our findings demonstrate that local biomaterial-based delivery of HGF hydrogel to injured cervical spinal cord is an effective strategy for preserving respiratory circuitry and diaphragm function.
-
Journal of neurotrauma · Aug 2024
Acute Development of Traumatic Intracranial Aneurysms Following Civilian Gunshot Wounds to the Head.
In previous studies, the incidence of traumatic intracranial aneurysms (TICAs) after civilian gunshot wound to the head (cGSWH) was ∼3%. Given the use of delayed vessel imaging, we hypothesize that a significant fraction of TICAs is missed on initial non-contrasted scans. This study was designed to characterize acute TICAs using admission computed tomographic angiography (aCTA) in cGSWH. ⋯ Nearly 30% of patients had spontaneous resolution within 1 week. When CTA was performed acutely, TICAs were 10 times more frequent in cGSWH than in previous literature, and those patients were more likely to proceed to surgery. Almost one third of patients in this series died from the devastating effects of cGSWH.
-
Journal of neurotrauma · Aug 2024
ReviewVisual Impairment in Preclinical Models of Mild Traumatic Brain Injury.
Impairment in visual function is common after traumatic brain injury (TBI) in the clinical setting, a phenomenon that translates to pre-clinical animal models as well. In Morris et al. (2021), we reported histological changes following weight-drop-induced TBI in a rodent model including retinal ganglion cell (RGC) loss, decreased electroretinogram (ERG) evoked potential, optic nerve diameter reduction, induced inflammation and gliosis, and loss of myelin accompanied by markedly impaired visual acuity. ⋯ This underscores the importance of understanding the role of the visual system and the potential detrimental sequelae to this sensory modality post-TBI. Given that most commonly employed behavioral tests such as the Elevated Plus Maze and Morris Water Maze rely on an intact visual system, interpretation of functional deficits in diffuse models may be confounded by off- target effects on the visual system.