Brain research
-
Vascular permeability and hemodynamic alteration in response to the transplantation of human bone marrow stromal cells (hMSCs) after traumatic brain injury (TBI) were longitudinally investigated in non directly injured and normal-appearing cerebral tissue using magnetic resonance imaging (MRI). Male Wistar rats (300-350g, n=30) subjected to controlled cortical impact TBI were intravenously injected with 1ml of saline (at 6-h or 1-week post-injury, n=5/group) or with hMSCs in suspension (∼3×106 hMSCs, at 6-h or 1-week post-injury, n=10/group). MRI measurements of T2-weighted imaging, cerebral blood flow (CBF) and blood-to-brain transfer constant (Ki) of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), and neurological behavioral estimates were performed on all animals at multiple time points up to 3-months post-injury. ⋯ Our data reveal a sensitive vascular permeability and hemodynamic reaction in response to the time-dependent transplantation of hMSCs. A more rapid reduction of Ki following cell treatment is associated with a higher level of CBF in the injured brain, and acute (6h) cell administration leads to enhanced therapeutic effects on both the recovery of vascular integrity and stabilization of cerebral perfusion compared to delayed (1w) cell engraftment. Our results indicate that cell-enhanced BBB reconstitution plays an important role in underlying the restoration of CBF in the injured brain, which in turn, contributes to the improvement of functional outcome.
-
Status epilepticus (SE, a prolonged seizure activity) is a high risk factor of developing vasogenic edema, which leads to secondary complications following SE. In the present study, we investigated whether transient receptor potential canonical channel-3 (TRPC3) may link vascular endothelial growth factor (VEGF) pathway to NFκB/ETB receptor axis in the rat piriform cortex during vasogenic edema formation. Following SE, TRPC3 and ETB receptor independently activated phosphatidylinositol 3 kinase (PI3K)/AKT/eNOS signaling pathway. ⋯ These findings indicate that PI3K/AKT may be common down-stream molecules for TRPC3- and ETB receptor signaling pathways during vasogenic edema formation. In addition, the present data demonstrate for the first time that TRPC3 may integrate VEGF- and NFκB-mediated vasogenic edema formation following SE. Thus, we suggest that PI3K/AKT signaling pathway may be one of considerable therapeutic targets for vasogenic edema.
-
Hypothermia has demonstrated neuroprotection following ischemia in preclinical studies while its clinical application is still very limited. The aim of this study was to explore whether combining local hypothermia in ischemic territory achieved by intra-arterial cold infusions (IACIs) with pharmacologically induced hypothermia enhances therapeutic outcomes, as well as the underlying mechanism. ⋯ The combination approach is able to enhance the efficiency of hypothermia and efficacy of hypothermia-induced neuroprotection following ischemic stroke. The findings here move us a step closer towards translating this long recognized TH from bench to bedside.
-
Traumatic brain injury (TBI) contributes to morbidity in children, and more boys experience TBI. Cerebral autoregulation is impaired after TBI, contributing to poor outcome. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP). ⋯ These data indicate that DA protects autoregulation and limits hippocampal neuronal cell necrosis via block of ERK after FPI in male and female juvenile pigs. Of the vasoactive agents prior investigated, including norepinephrine, epinephrine, and phenylephrine, DA is the only one demonstrated to improve outcome after TBI in both sexes and ages. These data suggest that DA should be considered as a first line treatment to protect cerebral autoregulation and promote cerebral outcomes in pediatric TBI irrespective of age and sex.
-
Acute subdural hematoma (ASDH) is a frequent complication of severe head injury, whose secondary ischemic lesions are often responsible for the severity of the disease. We focused on the differences of secondary ischemic lesions caused by the components, 0.4ml venous- or arterial-blood, or saline, infused in the subdural space, evaluating the differences in vivo model, using rats. The saline infused rats are made for elderly atrophic brain with subdural effusion (SDE) model. ⋯ This study is the first study, in which different fluids in rats' subdural space, ASDH or SDE are compared with the extension of early and delayed brain damage by measuring brain edema and histological lesion volume. Blood constituents started to affect the degree of ischemia underneath the subdural hemorrhage, leading to more pronounced breakdown of the blood-brain barrier and brain damage. This indicates that further strategies to treat blood-dependent effects more efficiently are in view for patients with ASDH.