Traumatic brain injury (TBI) frequently results in neuroinflammation, which includes the invasion of neutrophils. After TBI, neutrophils infiltrate choroid plexus (CP), a site blood—cerebrospinal fluid (CSF) barrier (BCSFB), and accumulate CSF space near injury, from where these inflammatory cells may migrate to parenchyma. We have hypothesized that CP functions as an entry point for invade injured brain. Using controlled cortical impact model TBI rats vitro BCSFB, we show produces CXC...

The invasion of inflammatory cells occurring after ischemic or traumatic brain injury (TBI) has a detrimental effect on neuronal survival and functional recovery injury. We have recently demonstrated that not only the blood-brain barrier, but also blood-cerebrospinal fluid (CSF) barrier (BCSFB), role in posttraumatic recruitment neutrophils. Here, we show TBI results rapid increase synthesis release into CSF major chemoattractant for monocytes, CCL2, by choroid plexus epithelium, site BCSFB....

Arginine vasopressin (AVP) has previously been shown to promote disruption of the blood−brain barrier, exacerbate edema, and augment loss neural tissue in various forms models brain injury. However, mechanisms underlying these AVP actions are not well understood. These were studied AVP-deficient Brattleboro rats (Avpdi/di), their parental Long-Evans strain, using a controlled cortical impact model traumatic injury (TBI). The increased influx inflammatory cells into injured cortex wild-type...

No routine tests currently exist to objectively diagnose mild traumatic brain injury (mTBI)/concussion. Previously reported biomarkers for mTBI represented proteins released from damaged neurons or glia. However, low levels of these proteins, and/or the complexity assays used their detection, limits implementation in practice. Here, we sought identify whose synthesis is altered post-mTBI and blood could be measured using standard immunoassays. Adult patients sustaining a concussion within...

Upregulation of certain growth factors in the central nervous system can alter brain fluid dynamics. Hydrocephalus was produced adult Sprague-Dawley rats by infusing recombinant basic fibroblast factor (FGF-2) at 1 μg/day into a lateral ventricle for 2, 3, 5, or 10–12 days. Lateral and third ventricular enlargement progressively increased from 2 to 10 Ventriculomegaly also induced 75% reduced dose FGF-2. At days, there 29% attenuation cerebrospinal (CSF) formation rate, 2.5 1.8 μl/min ( P...

The cerebrospinal fluid (CSF)-generating choroid plexus (CP) has many V 1 binding sites for arginine vasopressin (AVP). AVP decreases CSF formation rate and choroidal blood flow, but little is known about how alters ion transport across the blood-CSF barrier. Adult rat lateral ventricle CP was loaded with 36 Cl − , exposed to 20 min, then placed in isotope-free artificial measure release of . Effect at 10 −12 −7 M on efflux coefficient (in s −1 ) quantified. Maximal inhibition (by 20%)...

Experimental evidence obtained in various animal models of brain injury indicates that vasopressin promotes the formation cerebral edema. However, molecular and cellular mechanisms underlying this action are not fully understood. In present study, we analyzed temporal changes expression V1a receptors after traumatic (TBI) rats. intact brain, receptor was expressed neurons located all layers frontoparietal cortex. The receptor-immunoreactive product predominantly localized to neuronal nuclei...

In a number of stress conditions, the biological effects tumor necrosis factor–α (TNF-α), such as induction neuronal apoptosis, are presumably attenuated by soluble fragments TNF receptors (sTNFRs). Within 1 h after spinal cord injury, increased synthesis and/or secretion TNF-α is detectable at injury site. However, shedding ectodomains TNFRs in traumatized has not yet been reported. present study, adult Sprague-Dawley rats were subjected to acute (ASCI) applying 25-g Walsh-Tator aneurysm...

There is an increasing interest in using choroid plexus (CP) epithelial cell lines to study the properties of blood-cerebrospinal fluid barrier (BCSFB). Currently, there are three major CP-derived available. Z310 and TR-CSFB3, two immortalized carrying simian virus 40 large T-antigen gene, were derived from rat CP epithelium, whereas CPC-2 line was human carcinoma. Although these have previously been used various functional studies, expression adherens junction (AJ) tight (TJ) proteins cells...

Several lines of evidence indicate that the blood-cerebrospinal fluid barrier (BCSFB), which primarily resides in choroid plexus (CP), plays a significant pathophysiological role not only neuroinflammatory diseases, such as multiple sclerosis, but also traumatic brain injury (TBI). Here we investigated how arginine vasopressin (AVP) regulates function BCSFB context post-traumatic neuroinflammation. It has previously been shown AVP exacerbates various forms injury, mechanisms underlying this...

Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, peptidomimetic ligand which targets the scaffold protein, postsynaptic density protein 95, to enhance downstream tropomyosin-related kinase B, receptor for BDNF, can improve neurological function after TBI....

Background and objective Matrix metalloproteinases (MMPs) mediate blood–brain barrier dysfunction in inflammatory disease states. Our was to compare circulating MMPs children with diabetic ketoacidosis (DKA) type 1 diabetes mellitus without DKA. Research design methods This a prospective study performed at five tertiary-care pediatric hospitals. We measured plasma MMP-2, MMP-3, MMP-9 early during DKA (time 1; within 2 h of beginning intravenous fluids) therapy 2; median 8 h; range: 4–16 h)....

Previous studies have indicated that the primary targets for vasopressin actions on injured brain are cerebrovascular endothelium and astrocytes, amplifies posttraumatic production of proinflammatory mediators. Here, controlled cortical impact model traumatic injury in rats was used to identify sources brain. Injury increased synthesis hypothalamus cerebral cortex adjacent lesion. In cortex, predominantly produced by activated microglia/macrophages, and, a lesser extent, endothelium. These...

The pathophysiological mechanisms underlying mild traumatic brain injury (mTBI) are not well understood, but likely involve neuroinflammation. Here the controlled cortical impact model of mTBI in rats was used to test this hypothesis. Mild TBI caused a rapid (within 6 h post-mTBI) upregulation synthesis TNF-α and IL-1β cerebral cortex hippocampus, followed by an increase production neutrophil (CXCL1-3) monocyte (CCL2) chemoattractants. While astrocytes were significant source CXC chemokines,...

Neuroinflammation and dysfunction of the blood-brain barrier (BBB) are two prominent mechanisms secondary injury in neurotrauma. It has been suggested that Toll-like receptors (TLRs) play important roles initiating propagating neuroinflammation resulting from traumatic brain (TBI), but potential beneficial effects targeting these TBI have not broadly studied. Here, we investigated effect TLRs with proteoglycan 4 (PRG4) on post-traumatic BBB function. PRG4 is a mucinous glycoprotein strong...

Postnatal developmental changes in blood flow to choroid plexuses of the lateral (LVCP) and fourth (4VCP) ventricles cerebral cortex were studied pentobarbital-anesthetized rats at 2, 3, 5, 7-8 wk. Blood was measured by indicator fractionation with N-isopropyl-p-[125I]iodoamphetamine as marker. LVCP 4VCP 2.5 +/- 0.1 2.7 ml.g-1.min-1, respectively, did not change between 2nd 3rd However, it increased 34% 5th From age 5 wk on, characterized higher rates than LVCP. Cerebral cortical gradually...

GPR125 belongs to the family of Adhesion G protein-coupled receptors (GPCRs). A single copy was found in many vertebrate genomes. We also identified a Drosophila sequence, DmCG15744, which shares common ancestor with entire Group III GPCRs, and contains Ig, LRR HBD domains were observed mammalian GPR125. specific expression cells choroid plexus using situ hybridization protein-specific antibodies combined situ/immunohistochemistry co-localization cytokeratin, marker for epithelial cells....