Journal of neurotrauma
-
Journal of neurotrauma · Feb 2018
Treatment of traumatic brain injury with vepoloxamer (Purified Poloxamer 188).
Vepoloxamer is an amphipathic polymer that has shown potent hemorrheologic, cytoprotective, and anti-inflammatory effects in both pre-clinical and clinical studies. This study was designed to investigate the therapeutic effects of vepoloxamer on sensorimotor and cognitive functional recovery in rats after traumatic brain injury (TBI) induced by controlled cortical impact. Young adult male Wistar rats were randomly divided into the following groups: 1) sham; 2) saline; or 3) vepoloxamer. ⋯ Compared with the saline treatment, vepoloxamer initiated 2 h post-injury significantly improved sensorimotor functional recovery (Days 1-35; p < 0.0001) and spatial learning (Days 32-35; p < 0.0001), reduced cortical lesion volume by 20%, and reduced activation of microglia/macrophages and astrogliosis in many brain regions including injured cortex, corpus callosum, and hippocampus, as well as normalized the bleeding time and reduced brain hemorrhage and microthrombosis formation. In summary, vepoloxamer treatment initiated 2 h post-injury provides neuroprotection and anti-inflammation in rats after TBI and improves functional outcome, indicating that vepoloxamer treatment may have potential value for treatment of TBI. Further investigation of the optimal dose and therapeutic window of vepoloxamer treatment for TBI and the mechanisms underlying beneficial effects are warranted.
-
Journal of neurotrauma · Feb 2018
A time limit for starting anti-inflammatory treatment for better improvement of olfactory dysfunction after head injury.
We previously reported that treatment with an anti-inflammatory drug, specifically a steroid, is effective in improving recovery during the acute phase of head injury. Clinically, however, patients with head injury usually become aware of their olfactory loss several weeks or months after the injury, which may be a critical factor in poor recovery from olfactory dysfunction. This raises an important question: When should steroid administration begin in order to achieve optimum improvement of olfactory dysfunction? The present study was designed to reveal the time limit for starting anti-inflammatory treatment for better improvement of post-traumatic olfactory dysfunction. ⋯ Animals treated at 7 days post-injury had less injury-associated tissue with fewer astrocytes and macrophages and better histological and functional nerve recovery, compared with control mice. However, those treated at 14, 28, or 42 days post-injury did not show significant histological or functional differences between saline control and treatment groups. These findings suggest that an anti-inflammatory treatment using steroids for traumatic olfactory dysfunction may be effective if started at least by 7 days, but may be ineffective at 14 days or later after head injury.
-
Journal of neurotrauma · Feb 2018
Observational StudyEffect of History of Mild Traumatic Brain Injury on Optic Nerve Sheath Diameter Changes after Valsalva Maneuver.
Optic nerve sheath diameter (ONSD) measured by transocular ultrasound is a marker of real-time intracranial pressure (ICP). The objective of this study was to evaluate the association between optic nerve sheath (ONS) dilation after a Valsalva maneuver and a prior history of mild to moderate traumatic brain injury (mTBI) in a heterogeneous sample of participants. Participants were excluded if they had had a recent brain injury, were symptomatic from a prior brain injury, had a history consistent with severe TBI and/or had undergone intracranial surgery. ⋯ Following Valsalva, participants with a history of mTBI had a statistically significant increase in the ONSD compared with participants with no history of mTBI. This significant difference persisted after controlling for age, race, and sex. This study demonstrated an association between a prior history of mTBI and dilation of the ONS after Valsalva maneuver in a sample of asymptomatic participants, which was not seen in participants without a history of mTBI.
-
Journal of neurotrauma · Feb 2018
Exacerbation of Acute Traumatic Brain Injury by Circulating Extracellular Vesicles.
Inflammatory lesions in the brain activate a systemic acute-phase response (APR), which is dependent on the release of extracellular vesicles (EVs) into the circulation. The resulting APR is responsible for regulating leukocyte mobilization and subsequent recruitment to the brain. Factors that either exacerbate or inhibit the APR will also exacerbate or inhibit central nervous system (CNS) inflammation as a consequence and have the potential to influence ongoing secondary damage. ⋯ By manipulating the circulating EV population, we were able to demonstrate that each population of transferred EVs increased the APR. However, the characteristics of the response were dependent on the nature of the EVs; specifically, it was significantly increased when animals were challenged with macrophage-derived EVs, suggesting that the cellular origins of EVs may determine their function. Selectively targeting EVs from macrophage/monocyte populations is likely to be of value in reducing the impact of the systemic inflammatory response on the outcome of traumatic CNS injury.
-
Journal of neurotrauma · Feb 2018
Erythropoietin Attenuates the Brain Edema Response after Experimental Traumatic Brain Injury.
Erythropoietin (EPO) has neuroprotective effects in multiple central nervous system (CNS) injury models; however EPO's effects on traumatic brain edema are elusive. To explore EPO as an intervention in traumatic brain edema, male Sprague-Dawley (SD) rats were subjected to blunt, controlled traumatic brain injury (TBI). Animals were randomized to EPO 5000 IU/kg or saline (control group) intraperitoneally within 30 min after trauma and once daily for 4 consecutive days. ⋯ Animals treated with EPO demonstrated conserved levels of aquaporin 4 (AQP4) protein expression in the perilesional area, whereas control animals showed a reduction of AQP4. We show that post TBI administration of EPO decreases early cytotoxic brain edema and preserves structural and functional properties of the BBB, leading to attenuation of the vasogenic edema response. The data support that the mechanisms involve preservation of the tight junction protein ZO-1 and the water channel AQP4, and indicate that treatment with EPO may have beneficial effects on the brain edema response following TBI.