Journal of neurotrauma
-
Journal of neurotrauma · Jan 2017
Hemolysed blood elicits - calcium antagonist and high CO2 reversible - constrictions via elevation of Ca2+ in isolated cerebral arteries.
During acute subarachnoid hemorrhage, blood is hemolyzed, which is followed by a significant cerebrovascular spasm resulting in a serious clinical condition. Interestingly, however, the direct vasomotor effect of perivascular hemolyzed blood (HB) has not yet been characterized, preventing the assessment of contribution of vasoconstrictor mechanisms deriving from brain tissue and/or blood and development of possible treatments. We hypothesized that perivascular HB reduces the diameter of the cerebral arteries (i.e., basilar artery [BA]; middle cerebral artery [MCA]) by elevating vascular tissue [Ca2+]i level. ⋯ After washout of HB, nitric oxide-mediated dilations remained significantly reduced compared to control. HB significantly increased the ratiometric Ca signal, which returned to control level after washout. In conclusion, perivascular hemolyzed blood elicits significant-nifedipine and high CO2 reversible-constrictions of isolated BAs and MCAs, primarily by increasing intracellular Ca2+, findings that can contribute to the refinement of local treatment of subarachnoid hemorrhage.
-
Journal of neurotrauma · Jan 2017
Comprehensive Profiling of Modulation of Nitric Oxide levels and Mitochondrial Activity in Injured Brain: An Experimental Study based on the Fluid Percussion Injury Model in Rats.
Nitric oxide (NO) has frequently been associated with secondary damage after brain injury. However, average NO levels in different brain regions before and after traumatic brain injury (TBI) and its role in post-TBI mitochondrial dysfunction remain unclear. In this comprehensive profiling study, we demonstrate for the first time that basal NO levels vary significantly in the healthy cortex (0.44 ± 0.04 μM), hippocampus (0.26 ± 0.03 μM), and cerebellum (1.24 ± 0.08 μM). ⋯ NO-mediated impairment of mitochondrial state 3 respiration dependent on complex I substrates was transient and confined to the ipsilateral cortex. Our results demonstrate that NO dynamics and associated effects differ in various regions of the injured brain. A potential association between the observed mitochondrial electron flow through complex I, but not complex II, and the modulation of TBI induced NO levels in different brain regions has to be prospectively analyzed in more detail.
-
Journal of neurotrauma · Jan 2017
Diffusion-derived MRI Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after TBI.
Using magnetic resonance imaging (MRI) and an animal model of traumatic brain injury (TBI), we investigated the capacity and sensitivity of diffusion-derived measures, fractional anisotropy (FA), and diffusion entropy, to longitudinally identify structural plasticity in the injured brain in response to the transplantation of human bone marrow stromal cells (hMSCs). Male Wistar rats (300-350g, n = 30) were subjected to controlled cortical impact TBI. At 6 h or 1 week post-injury, these rats were intravenously injected with 1 mL of saline (at 6 h or 1 week, n = 5/group) or with hMSCs in suspension (∼3 × 106 hMSCs, at 6 h or 1 week, n = 10/group). ⋯ Our data demonstrate that administration of hMSCs after TBI leads to enhanced white matter reorganization particularly along the boundary of contusional lesion, which can be identified by both FA and entropy. Compared with the therapy performed at 1 week post-TBI, cell intervention executed at 6 h expedites the brain remodeling process and results in an earlier functional recovery. Although FA and entropy present a similar capacity to dynamically detect the microstructural changes in the tissue regions with predominant orientation of fiber tracts, entropy exhibits a sensitivity superior to that of FA, in probing the structural alterations in the tissue areas with complex fiber patterns.
-
Journal of neurotrauma · Jan 2017
Variation in PPP3CC genotype is associated with long-term recovery after severe brain injury.
After experimental traumatic brain injury (TBI), calcineurin is upregulated; blocking calcineurin is associated with improved outcomes. In humans, variation in the calcineurin A-gamma gene (PPP3CC) has been associated with neuropsychiatric disorders, though any role in TBI recovery remains unknown. This study examines associations between PPP3CC genotype and mortality, as well as gross functional status assessed at admission using the Glasgow Coma Scale (GCS) and at 3, 6, and 12 months after severe TBI using the Glasgow Outcome Score (GOS). ⋯ The rs2443504 AA genotype was univariately associated with GCS (p = 0.022), GOS at 3, 6, and 12 months (p = 0.002, p = 0.034, and p = 0.004, respectively), and mortality (p = 0.007). In multivariate analysis controlling for age, sex, and GCS, the AA genotype of rs2443504 was associated with GOS at 3 (p = 0.02), and 12 months (p = 0.01), with a trend toward significance at 6 months (p = 0.05); the AA genotype also was associated with mortality in the multivariate model (p = 0.04). Further work is warranted to better understand the role of calcineurin, as well as the genes encoding it and their relevance to outcomes after brain injury.