Cognitive Effects of Astaxanthin Pretreatment on Recovery From Traumatic Brain Injury.

Traumatic brain injury (TBI), caused by mechanical impact to the brain, is a leading cause of death and disability among young adults, with slow and often incomplete recovery. Preemptive treatment strategies may increase the injury resilience of high-risk populations such as soldiers and athletes. In this work, the xanthophyll carotenoid Astaxanthin was examined as a potential nutritional preconditioning method in mice (sabra strain) to increase their resilience prior to TBI in a closed head injury (CHI) model.

Nerve growth factor plays a role in the neurotherapeutic effect of a CD45 pan-hematopoietic subpopulation derived from human umbilical cord blood in a traumatic brain injury model.

Background Aims: Human umbilical cord blood (HUCB) is an important source of stem cells for therapy of hematopoietic disorders and is a potential therapy for various neurological disorders, including traumatic brain injury (TBI). The expression of nerve growth factor (NGF) and its receptors TrkA, p75 and α9β1 integrin on an HUCB CD45 pan-hematopoietic subpopulation was investigated in the context of its neurotherapeutic potential after TBI.

Methods: NGF and its receptors were detected on CD45 cells by reverse transcriptase polymerase chain reaction, flow cytometry analysis and confocal microscopy.

Are the endocannabinoid-like compounds N-acyl aminoacids neuroprotective after traumatic brain injury?

In recent years, a library of approx. 70 N-acyl aminoacids (NAAAs) was discovered in the rat brain. A particular member of this family of compounds is arachidonoyl serine (AraS), which has generated special interest as a potential therapy for traumatic brain injury (TBI).

Palmitoyl Serine: An Endogenous Neuroprotective Endocannabinoid-Like Entity After Traumatic Brain Injury.

The endocannabinoid (eCB) system helps recovery following traumatic brain injury (TBI). Treatment with 2-arachidonoylglycerol (2-AG), a cerebral eCB ligand, was found to ameliorate the secondary damage. Interestingly, the fatty acid amino acid amide (FAAA) N-arachidonoyl-L-serine (AraS) exerts similar eCB dependent neuroprotective.

Angiotensin receptor type 2 activation induces neuroprotection and neurogenesis after traumatic brain injury.

Angiotensin II receptor type 2 (AT(2)) agonists have been shown to limit brain ischemic insult and to improve its outcome. The activation of AT(2) was also linked to induced neuronal proliferation and differentiation in vitro. In this study, we examined the therapeutic potential of AT(2) activation following traumatic brain injury (TBI) in mice, a brain pathology that displays ischemia-like secondary damages.

Neuroprotection after traumatic brain injury in heat-acclimated mice involves induced neurogenesis and activation of angiotensin receptor type 2 signaling.

Long-term exposure of mice to mild heat (34°C±1°C) confers neuroprotection against traumatic brain injury (TBI); however, the underling mechanisms are not fully understood. Heat acclimation (HA) increases hypothalamic angiotensin II receptor type 2 (AT2) expression and hypothalamic neurogenesis. Accumulating data suggest that activation of the brain AT2 receptor confers protection against several types of brain pathologies, including ischemia, a hallmark of the secondary injury occurring following TBI.

Neurotherapeutic effect of cord blood derived CD45+ hematopoietic cells in mice after traumatic brain injury.

Treatment of traumatic brain injury (TBI) is still an unmet need. Cell therapy by human umbilical cord blood (HUCB) has shown promising results in animal models of TBI and is under evaluation in clinical trials. HUCB contains different cell populations but to date, only mesenchymal stem cells have been evaluated for therapy of TBI.

Inosine improves functional recovery after experimental traumatic brain injury.

Despite years of research, no effective therapy is yet available for the treatment of traumatic brain injury (TBI). The most prevalent and debilitating features in survivors of TBI are cognitive deficits and motor dysfunction. A potential therapeutic method for improving the function of patients following TBI would be to restore, at least in part, plasticity to the CNS in a controlled way that would allow for the formation of compensatory circuits.

The role and dynamics of β-catenin in precondition induced neuroprotection after traumatic brain injury.

Preconditioning via heat acclimation (34°C 30 d) results in neuroprotection from traumatic brain injury due to constitutive as well as dynamic changes triggered by the trauma. Among these changes is Akt phosphorylation, which decreases apoptosis and induces HIF1α. In the present study we investigated the Akt downstream GSK3β/β-catenin pathway and focused on post injury alternations of β catenin and its impact on the cellular response in preconditioned heat acclimated mice.

N-arachidonoyl-L-serine (AraS) possesses proneurogenic properties in vitro and in vivo after traumatic brain injury.

N-arachidonoyl-L-serine (AraS) is a novel neuroprotective endocannabinoid. We aimed to test the effects of exogenous AraS on neurogenesis after traumatic brain injury (TBI). The effects of AraS on neural progenitor cells (NPC) proliferation, survival, and differentiation were examined in vitro.

Hypoxia-inducible factor 1 is essential for spontaneous recovery from traumatic brain injury and is a key mediator of heat acclimation induced neuroprotection.

Heat acclimation (HA), a well-established preconditioning model, confers neuroprotection in rodent models of traumatic brain injury (TBI). It increases neuroprotective factors, among them is hypoxia-inducible factor 1α (HIF-1α), which is important in the response to postinjury ischemia. However, little is known about the role of HIF-1α in TBI and its contribution to the establishment of the HA protecting phenotype.

Carvacrol together with TRPC1 elimination improve functional recovery after traumatic brain injury in mice.

Death of Central Nervous System (CNS) neurons following traumatic brain injury (TBI) is a complex process arising from a combination of factors, many of which are still unknown. It has been found that inhibition of transient receptor potential (TRP) channels constitutes an effective strategy for preventing death of CNS neurons following TBI. TRP channels are classified into seven related subfamilies, most of which are Ca(2+) permeable and involved in many cellular functions, including neuronal cell death.

Near infrared transcranial laser therapy applied at various modes to mice following traumatic brain injury significantly reduces long-term neurological deficits.

Near-infrared transcranial laser therapy (TLT) has been found to modulate various biological processes including traumatic brain injury (TBI). Following TBI in mice, in this study we assessed the possibility of various near-infrared TLT modes (pulsed versus continuous) in producing a beneficial effect on the long-term neurobehavioral outcome and brain lesions of these mice. TBI was induced by a weight-drop device, and neurobehavioral function was assessed from 1 h to 56 days post-trauma using the Neurological Severity Score (NSS).

The anti-inflammatory drug carprofen improves long-term outcome and induces gliogenesis after traumatic brain injury.

Traumatic brain injury (TBI) initiates acute and chronic inflammatory processes involving cyclooxygenase-2 (COX-2), which may have detrimental effects on outcome and especially on brain regeneration. Therefore we aimed to study whether carprofen, a COX-2 inhibitor, would improve outcome and increase neurogenesis after TBI. TBI was induced in Sabra mice that were then treated with vehicle or carprofen for 7 days.

N-arachidonoyl-L-serine is neuroprotective after traumatic brain injury by reducing apoptosis.

N-arachidonoyl-L-serine (AraS) is a brain component structurally related to the endocannabinoid family. We investigated the neuroprotective effects of AraS following closed head injury induced by weight drop onto the exposed fronto-parietal skull and the mechanisms involved. A single injection of AraS following injury led to a significant improvement in functional outcome, and to reduced edema and lesion volume compared with vehicle.

Regional sensitivity to neuroinflammation: in vivo and in vitro studies.

Background: Neuroinflammation is involved in several acute-onset neuropathologies such as meningitis, encephalitis, stroke, and traumatic brain injury as well as in neurodegenerative diseases. All of these patholologies are associated with cognitive deficits. Using a model of pure neuroinflammation (intracisternal injection of endotoxin in mice), we tested the hypothesis that brain regions involved in cognition are the most vulnerable to inflammatory insults, and this vulnerability is an inherent property of neocortical neurons.

D-cycloserine improves functional outcome after traumatic brain injury with wide therapeutic window.

It has been long thought that hyperactivation of N-methyl-D-aspartate (NMDA) receptors underlies neurological decline after traumatic brain injury. However, all clinical trials with NMDA receptor antagonists failed. Since NMDA receptors are down-regulated from 4h to 2weeks after brain injury, activation at 24h, rather than inhibition, of these receptors, was previously shown to be beneficial in mice.

Heat acclimation provides sustained improvement in functional recovery and attenuates apoptosis after traumatic brain injury.

Heat acclimation (HA) offers functional neuroprotection in mice after traumatic brain injury (TBI). This study further characterizes endogenous neuroprotection acquired by HA (34+/-1 degrees C, 30 d) after TBI. We establish here the ability of HA to induce sustained functional benefits and to reduce activation of apoptotic pathways.

CD38 facilitates recovery from traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. It causes progressive tissue atrophy and consequent neurological dysfunctions. TBI is accompanied by neuroinflammation, a process mediated largely by microglia.

Targeting cell death in vivo in experimental traumatic brain injury by a novel molecular probe.

Traumatic brain injury (TBI) remains a frequent and major challenge in neurological and neurosurgical practice. Apoptosis may play a role in cerebral tissue damage induced by the traumatic insult, and thus its detection and inhibition may advance patient care. DDC (N,N'-didansyl-L-cystine) is a novel fluorescent probe for detection of apoptotic cells.

Incensole acetate: a novel neuroprotective agent isolated from Boswellia carterii.

Boswellia resin has been used as a major anti-inflammatory agent and for the healing of wounds for centuries. Incensole acetate (IA), isolated from this resin, was shown to inhibit the activation of nuclear factor-kappaB, a key transcription factor in the inflammatory response. We now show that IA inhibits the production of inflammatory mediators in an in vitro model system of C6 glioma and human peripheral monocytes.

Dynamic changes in the recovery after traumatic brain injury in mice: effect of injury severity on T2-weighted MRI abnormalities, and motor and cognitive functions.

Memory and neurobehavioral dysfunctions are among the sequelae of traumatic brain injury (TBI). The Neurological Severity Score (NSS) includes 10 tasks and was previously designed to assess the functional status of mice after TBI. The object recognition task (ORT) measures specific episodic memory and is expressed by the percent time spent by an animal at a novel, unfamiliar object (Discrimination Index [DI]).

Altered cytokine expression and sustained hypothermia following traumatic brain injury in heat acclimated mice.

Long-term exposure to moderate ambient heat (heat acclimation, HA, 30 days at 34+/-1 degrees C) provides protection toward a variety of stressors including traumatic brain injury. As previous studies suggested an anti-inflammatory effect of HA and given the ability of augmented pre-injury anti-inflammatory cytokine expression to harbor neuroprotection and to attenuate early post-injury expression of pro-inflammatory mediators, we hypothesized that HA-induced neuroprotection may involve enhanced pre-injury expression of anti-inflammatory mediators or a reduction in post-injury TNF alpha (TNFalpha) expression. Since the attenuation of inflammatory-associated entities has also been linked to mild hypothermia, an established neuroprotective paradigm, the effect of HA on post-injury body temperature was also studied.