Increased cerebral uptake and oxidation of exogenous betaHB improves ATP following traumatic brain injury in adult rats

There is growing evidence of the brain's ability to increase its reliance on alternative metabolic substrates under conditions of energy stress such as starvation, hypoxia and ischemia. We hypothesized that following traumatic brain injury (TBI), which results in immediate changes in energy metabolism, the adult brain increases uptake and oxidation of the alternative substrate beta-hydroxybutyrate (betaHB). Arterio-venous differences were used to determine global cerebral uptake of betaHB and production of 14CO2 from [14C]3-betaHB 3 h after controlled cortical impact (CCI) injury. Quantitative bioluminescence was used to assess regional changes in ATP concentration. As expected, adult sham and CCI animals with only endogenously available betaHB showed no significant increase in cerebral uptake of betaHB or 14CO2 production. Increasing arterial betaHB concentrations 2.9-fold with 3 h of betaHB infusion failed to increase cerebral uptake of betaHB or 14CO2 production in adult sham animals. Only CCI animals that received a 3-h betaHB infusion showed an 8.5-fold increase in cerebral uptake of betaHB and greater than 10.7-fold increase in 14CO2 production relative to sham betaHB-infused animals. The TBI-induced 20% decrease in ipsilateral cortical ATP concentration was alleviated by 3 h of betaHB infusion beginning immediately after CCI injury.     

Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice

Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI.     

Influence of a brief episode of anesthesia during the induction of experimental brain trauma on secondary brain damage and inflammation

It is unclear whether a single, brief, 15-minute episode of background anesthesia already modulates delayed secondary processes after experimental brain injury. Therefore, this study was designed to characterize three anesthesia protocols for their effect on molecular and histological study endpoints. Mice were randomly separated into groups that received sevoflurane (sevo), isoflurane (iso) or an intraperitoneal anesthetic combination (midazolam, fentanyl and medetomidine; comb) prior to traumatic brain injury (controlled cortical impact, CCI; 8 m/s, 1 mm impact depth, 3 mm diameter). Twenty-four hours after insult, histological brain damage, neurological function (via neurological severity score), cerebral inflammation (via real-time RT-PCR for IL6, COX-2, iNOS) and microglia (via immunohistochemical staining for Iba1) were determined. Fifteen minutes after CCI, the brain contusion volume did not differ between the anesthetic regimens (sevo = 17.9±5.5 mm³; iso = 20.5±3.7 mm³; comb = 19.5±4.6 mm³). Within 24 hours after injury, lesion size increased in all groups (sevo = 45.3±9.0 mm³; iso = 31.5±4.0 mm³; comb = 44.2±6.2 mm³). Sevo and comb anesthesia resulted in a significantly larger contusion compared to iso, which was in line with the significantly better neurological function with iso (sevo = 4.6±1.3 pts.; iso = 3.9±0.8 pts.; comb = 5.1±1.6 pts.). The expression of inflammatory marker genes was not significantly different at 15 minutes and 24 hours after CCI. In contrast, significantly more Iba1-positive cells were present in the pericontusional region after sevo compared to comb anesthesia (sevo = 181±48/mm³; iso = 150±36/mm³; comb = 113±40/mm³). A brief episode of anesthesia, which is sufficient for surgical preparations of mice for procedures such as delivering traumatic brain injury, already has a significant impact on the extent of secondary brain damage.     

Preservation of the Blood Brain Barrier and Cortical Neuronal Tissue by Liraglutide,a Long Acting Glucagon-Like-1 Analogue,after Experimental Traumatic Brain Injury

Cerebral edema is a common complication following moderate and severe traumatic brain injury (TBI), and a significant risk factor for development of neuronal death and deterioration of neurological outcome. To this date, medical approaches that effectively alleviate cerebral edema and neuronal death after TBI are not available. Glucagon-like peptide-1 (GLP-1) has anti-inflammatory properties on cerebral endothelium and exerts neuroprotective effects. Here, we investigated the effects of GLP-1 on secondary injury after moderate and severe TBI. Male Sprague Dawley rats were subjected either to TBI by Controlled Cortical Impact (CCI) or sham surgery. After surgery, vehicle or a GLP-1 analogue, Liraglutide, were administered subcutaneously twice daily for two days. Treatment with Liraglutide (200 μg/kg) significantly reduced cerebral edema in pericontusional regions and improved sensorimotor function 48 hours after CCI. The integrity of the blood-brain barrier was markedly preserved in Liraglutide treated animals, as determined by cerebral extravasation of Evans blue conjugated albumin. Furthermore, Liraglutide reduced cortical tissue loss, but did not affect tissue loss and delayed neuronal death in the thalamus on day 7 post injury. Together, our data suggest that the GLP-1 pathway might be a promising target in the therapy of cerebral edema and cortical neuronal injury after moderate and severe TBI.     

Role of the Prostaglandin E2 EP1 Receptor in Traumatic Brain Injury

Brain injuries promote upregulation of so-called proinflammatory prostaglandins, notably prostaglandin E₂ (PGE₂), leading to overactivation of a class of its cognate G-protein-coupled receptors, including EP1, which is considered a promising target for treatment of ischemic stroke. However, the role of the EP1 receptor is complex and depends on the type of brain injury. This study is focused on the investigation of the role of the EP1 receptor in a controlled cortical impact (CCI) model, a preclinical model of traumatic brain injury (TBI). The therapeutic effects of post-treatments with a widely studied EP1 receptor antagonist, SC-51089, were examined in wildtype and EP1 receptor knockout C57BL/6 mice. Neurological deficit scores (NDS) were assessed 24 and 48 h following CCI or sham surgery, and brain immunohistochemical pathology was assessed 48 h after surgery. In wildtype mice, CCI resulted in an obvious cortical lesion and localized hippocampal edema with an associated significant increase in NDS compared to sham-operated animals. Post-treatments with the selective EP1 receptor antagonist SC-51089 or genetic knockout of EP1 receptor had no significant effects on cortical lesions and hippocampal swelling or on the NDS 24 and 48 h after CCI. Immunohistochemistry studies revealed CCI-induced gliosis and microglial activation in selected ipsilateral brain regions that were not affected by SC-51089 or in the EP1 receptor-deleted mice. This study provides further clarification on the respective contribution of the EP1 receptor in TBI and suggests that, under this experimental paradigm, the EP1 receptor would have limited effects in modulating acute neurological and anatomical pathologies following contusive brain trauma. Findings from this protocol, in combination with previous studies demonstrating differential roles of EP1 receptor in ischemic, neurotoxic, and hemorrhagic conditions, provide scientific background and further clarification of potential therapeutic application of prospective prostaglandin G-protein-coupled receptor drugs in the clinic for treatment of TBI and other acute brain injuries.     

Immediate, but not delayed, microsurgical skull reconstruction exacerbates brain damage in experimental traumatic brain injury model

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI.     

Controlled cortical impact injury affects dopaminergic transmission in the rat striatum

The therapeutic benefits of dopamine (DA) agonists after traumatic brain injury (TBI) imply a role for DA systems in mediating functional deficits post‐TBI. We investigated how experimental TBI affects striatal dopamine systems using fast scan cyclic voltammetry (FSCV), western blot, and d‐amphetamine‐induced rotational behavior. Adult male Sprague–Dawley rats were injured by a controlled cortical impact (CCI) delivered unilaterally to the parietal cortex, or were naïve controls. Amphetamine‐induced rotational behavior was assessed 10 days post‐CCI. Fourteen days post‐CCI, animals were anesthetized and underwent FSCV with bilateral striatal carbon fiber microelectrode placement and stimulating electrode placement in the medial forebrain bundle (MFB). Evoked DA overflow was assessed in the striatum as the MFB was electrically stimulated at 60 Hz for 10 s. In 23% of injured animals, but no naïve animals, rotation was observed with amphetamine administration. Compared with naïves, striatal evoked DA overflow was lower for injured animals in the striatum ipsilateral to injury (p < 0.05). Injured animals exhibited a decrease in V_max (52% of naïve, p < 0.05) for DA clearance in the hemisphere ipsilateral to injury compared with naïves. Dopamine transporter (DAT) expression was proportionally decreased in the striatum ipsilateral to injury compared with naïve animals (60% of naïve, p < 0.05), despite no injury‐related changes in vesicular monoamine transporter or D₂ receptor expression (DRD₂) in this region. Collectively, these data appear to confirm that the clinical efficacy of dopamine agonists in the treatment of TBI may be related to disruptions in the activity of subcortical dopamine systems.     

Frontal Lobe Contusion in Mice Chronically Impairs Prefrontal-Dependent Behavior

Traumatic brain injury (TBI) is a major cause of chronic disability in the world. Moderate to severe TBI often results in damage to the frontal lobe region and leads to cognitive, emotional, and social behavioral sequelae that negatively affect quality of life. More specifically, TBI patients often develop persistent deficits in social behavior, anxiety, and executive functions such as attention, mental flexibility, and task switching. These deficits are intrinsically associated with prefrontal cortex (PFC) functionality. Currently, there is a lack of analogous, behaviorally characterized TBI models for investigating frontal lobe injuries despite the prevalence of focal contusions to the frontal lobe in TBI patients. We used the controlled cortical impact (CCI) model in mice to generate a frontal lobe contusion and studied behavioral changes associated with PFC function. We found that unilateral frontal lobe contusion in mice produced long-term impairments to social recognition and reversal learning while having only a minor effect on anxiety and completely sparing rule shifting and hippocampal-dependent behavior.     

Mitochondrial dysfunction early after traumatic brain injury in immature rats

Mitochondria play central roles in acute brain injury; however, little is known about mitochondrial function following traumatic brain injury (TBI) to the immature brain. We hypothesized that TBI would cause mitochondrial dysfunction early (<4 h) after injury. Immature rats underwent controlled cortical impact (CCI) or sham injury to the left cortex, and mitochondria were isolated from both hemispheres at 1 and 4 h after TBI. Rates of phosphorylating (State 3) and resting (State 4) respiration were measured with and without bovine serum albumin. The respiratory control ratio was calculated (State 3/State 4). Rates of mitochondrial H(2)O(2) production, pyruvate dehydrogenase complex enzyme activity, and cytochrome c content were measured. Mitochondrial State 4 rates (ipsilateral/contralateral ratios) were higher after TBI at 1 h, which was reversed with bovine serum albumin. Four hours after TBI, pyruvate dehydrogenase complex activity and cytochrome c content (ipsilateral/contralateral ratios) were lower in TBI mitochondria. These data demonstrate abnormal mitochondrial function early (相似文献   

清醒小鼠严重颅脑闭合性撞击伤模型的建立

目的-建立一种清醒小鼠严重颅脑闭合性撞击伤模型, 模拟交通事故和战伤中的清醒致伤过程, 为相关研究创造新的动物模型基础。方法-将雄性KM小鼠头戴钢盔后清醒固定, 用BIM III型小型多功能动物撞击机击打, 致伤后2 h、8 h、24 h、48 h、72 h、120 h、1 w、2 w进行神经行为学评分、运动功能评分、死亡小鼠脑组织和肺组织水含量、死亡率、病理切片和电镜观察。结果-致伤后 48 h内致伤组运动功能评分、神经行为学评分明显低于对照组 (P<0 05); 致伤后死亡率高, 各组死亡小鼠脑组织水含量无明显差异, 但致伤组肺组织水含量明显高于对照组 (P <0 05); 病理切片和电镜检查显示, 致伤后脑组织细胞肿胀、坏死。结论-基本成功建立了模拟交通事故和战伤的清醒小鼠严重颅脑闭合性撞击伤模型。     

Absence of TLR4 Reduces Neurovascular Unit and Secondary Inflammatory Process after Traumatic Brain Injury in Mice

Background

Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. Toll-like receptors (TLRs) are signaling receptors in the innate immune system, although emerging evidence indicates their role in brain injury. We have therefore investigated the role played by TLR4 signaling pathway in the development of mechanisms of secondary inflammatory process in traumatic brain injury (TBI) differ in mice that lack a functional TLR4 signaling pathway.

Methods/Principal Findings

Controlled cortical impact injury was performed on TLR4 knockout (KO) mice (C57BL/10ScNJ) and wild-type (WT) mice (C57BL/10ScNJ). TBI outcome was evaluated by determination of infarct volume and assessment of neurological scores. Brains were collected at 24 h after TBI. When compared to WT mice, TLR4 KO mice had lower infarct volumes and better outcomes in neurological and behavioral tests (evaluated by EBST and rotarod test). Mice that lacked TLR4 had minor expression of TBI-induced GFAP, Chymase, Tryptase, IL-1β, iNOS, PARP and Nitrotyrosine mediators implicated in brain damage. The translocation of expression of p-JNK, IκB-α and NF-κB pathway were also lower in brains from TLR4 KO mice. When compared to WT mice, resulted in significant augmentation of all the above described parameters. In addition, apoptosis levels in TLR4 KO mice had minor expression of Bax while on the contrary with Bcl-2.

Conclusions/Significance

Our results clearly demonstrated that absence of TLR4 reduces the development of neuroinflammation, tissues injury events associated with brain trauma and may play a neuroprotective role in TBI in mice.     

Ceruloplasmin and β-amyloid precursor protein confer neuroprotection in traumatic brain injury and lower neuronal iron

Traumatic brain injury (TBI) is in part complicated by pro-oxidant iron elevation independent of brain hemorrhage. Ceruloplasmin (CP) and β-amyloid protein precursor (APP) are known neuroprotective proteins that reduce oxidative damage through iron regulation. We surveyed iron, CP, and APP in brain tissue from control and TBI-affected patients who were stratified according to time of death following injury. We observed CP and APP induction after TBI accompanying iron accumulation. Elevated APP and CP expression was also observed in a mouse model of focal cortical contusion injury concomitant with iron elevation. To determine if changes in APP or CP were neuroprotective we employed the same TBI model on APP^−/− and CP^−/− mice and found that both exhibited exaggerated infarct volume and iron accumulation postinjury. Evidence supports a regulatory role of both proteins in defence against iron-induced oxidative damage after TBI, which presents as a tractable therapeutic target.     

Effects of over‐expression of HIF‐1alpha in bone marrow‐derived mesenchymal stem cells on traumatic brain injury

Mesenchymal stem cells (MSCs) have been shown to play therapeutic effect in traumatic brain injury (TBI). To augment the therapeutic effect, MSCs could be engineered to over‐express genes that are beneficial for treatment. In the present study, we over‐expressed hypoxia inducible factor (HIF)‐1alpha in bone marrow derived MSCs (BM‐MSCs) and sought to investigate whether HIF‐1alpha could enhance the therapeutic effect of MSCs in a mouse model of TBI. Balb/c mice were subjected to controlled cortical impact injury and MSCs were transplanted intravenously at 6 h after injury. The lesion volume and brain water content were measured and the neurological function was assessed by modified neurologic severity score tests. Double‐labeled immunofluorescence for BrdU and NeuU was performed to determine angiogenesis and neurogenesis. The expression of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) was measured by quantitative RT‐PCR and western blotting. After TBI, mice received BM‐MSCs over‐expressing HIF‐1alpha showed significantly more functional recovery, reduced brain damage, increased angiogenesis and neurogenesis and increased expression of VEGF and EPO, compared with control mice or mice treated with non‐transduced BM‐MSCs. Over‐expression of HIF‐1alpha enhanced BM‐MSCs induced improvement of neurological recovery after TBI, by stimulating angiogenesis and neurogenesis.     

Effect of melatonin on brain oxidative damage induced by traumatic brain injury in immature rats

Progressive compromise of antioxidant defenses and free radical-mediated lipid peroxidation, which is one of the major mechanisms of secondary traumatic brain injury (TBI), has also been reported in pediatric head trauma. In the present study, we aimed to demonstrate the effect of melatonin, which is a potent free radical scavenger, on brain oxidative damage in 7-day-old rat pups subjected to contusion injury. Whereas TBI significantly increased thiobarbituric acid reactive substances (TBARS) levels, there was no compensatory increase in the antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) 24 hours after TBI in 7-day-old rats. Melatonin administered as a single dose of 5 mg/kg prevented the increase in TBARS levels in both non-traumatized and traumatized brain hemispheres. In conclusion, melatonin protects against oxidative damage induced by TBI in the immature brain.     

Immune Senescence: Relative Contributions of Age and Cytomegalovirus Infection

Immune senescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterised by impaired protective immunity and decreased efficacy of vaccines. Recent clinical, epidemiological and immunological studies suggest that Cytomegalovirus (CMV) infection may be associated with accelerated immune senescence, possibly by restricting the naïve T cell repertoire. However, direct evidence whether and how CMV-infection is implicated in immune senescence is still lacking. In this study, we have investigated whether latent mouse CMV (MCMV) infection with or without thymectomy (Tx) alters antiviral immunity of young and aged mice. After infection with lymphocytic choriomeningitis virus (LCMV) or Vaccinia virus, specific antiviral T cell responses were significantly reduced in old, old MCMV-infected and/or Tx mice compared to young mice. Importantly, control of LCMV replication was more profoundly impaired in aged MCMV-infected mice compared to age-matched MCMV-naïve or young mice. In addition, latent MCMV infection was associated with slightly reduced vaccination efficacy in old Tx mice. In contrast to the prevailing hypothesis of a CMV-mediated restriction of the naïve T cell repertoire, we found similar naïve T cell numbers in MCMV-infected and non-infected mice, whereas ageing and Tx clearly reduced the naïve T cell pool. Instead, MCMV-infection expanded the total CD8⁺ T cell pool by a massive accumulation of effector memory T cells. Based on these results, we propose a new model of increased competition between CMV-specific memory T cells and any ‘de novo’ immune response in aged individuals. In summary, our results directly demonstrate in a mouse model that latent CMV-infection impairs immunity in old age and propagates immune senescence.     

Volatile Anesthetics Influence Blood-Brain Barrier Integrity by Modulation of Tight Junction Protein Expression in Traumatic Brain Injury

Disruption of the blood-brain barrier (BBB) results in cerebral edema formation, which is a major cause for high mortality after traumatic brain injury (TBI). As anesthetic care is mandatory in patients suffering from severe TBI it may be important to elucidate the effect of different anesthetics on cerebral edema formation. Tight junction proteins (TJ) such as zonula occludens-1 (ZO-1) and claudin-5 (cl5) play a central role for BBB stability. First, the influence of the volatile anesthetics sevoflurane and isoflurane on in-vitro BBB integrity was investigated by quantification of the electrical resistance (TEER) in murine brain endothelial monolayers and neurovascular co-cultures of the BBB. Secondly brain edema and TJ expression of ZO-1 and cl5 were measured in-vivo after exposure towards volatile anesthetics in native mice and after controlled cortical impact (CCI). In in-vitro endothelial monocultures, both anesthetics significantly reduced TEER within 24 hours after exposure. In BBB co-cultures mimicking the neurovascular unit (NVU) volatile anesthetics had no impact on TEER. In healthy mice, anesthesia did not influence brain water content and TJ expression, while 24 hours after CCI brain water content increased significantly stronger with isoflurane compared to sevoflurane. In line with the brain edema data, ZO-1 expression was significantly higher in sevoflurane compared to isoflurane exposed CCI animals. Immunohistochemical analyses revealed disruption of ZO-1 at the cerebrovascular level, while cl5 was less affected in the pericontusional area. The study demonstrates that anesthetics influence brain edema formation after experimental TBI. This effect may be attributed to modulation of BBB permeability by differential TJ protein expression. Therefore, selection of anesthetics may influence the barrier function and introduce a strong bias in experimental research on pathophysiology of BBB dysfunction. Future research is required to investigate adverse or beneficial effects of volatile anesthetics on patients at risk for cerebral edema.     

Presence of DNA fragmentation and lack of neuroprotective effect in DFF45 knockout mice subjected to traumatic brain injury

BACKGROUND: Apoptosis plays an important pathophysiologic role in neuronal cell loss and associated neurologic deficits following traumatic brain injury (TBI). DNA fragmentation represents one of the characteristic biochemical features of neuronal apoptosis and is observed after experimental TBI. DFF45 and DFF40 are essential for DNA fragmentation in various models of apoptosis. MATERIALS AND METHODS: We used mice deficient in DFF45 and wild-type controls. Oligonucleosomal DNA fragmentation induced by TBI was analyzed using in vivo and in vitro assays. Expression and integrity of DFF45 and DFF40 proteins was assessed by Western analysis. Other outcome measurements included neurologic scoring, learning/memory tests, lesion volume measurements (MRI), and assessment of cell viability in vitro among others. RESULTS: We compared the effects of controlled cortical impact (CCI) trauma in DFF45 knockout mice and wild-type controls. Analysis of TBI-induced DNA fragmentation in brain cortex from wild-type and DFF45 knockout mice indicates that, although somewhat delayed, oligonucleosomal cleavage of DNA occurs after TBI in DFF45 knockout mice. DFF45 knockouts showed no significant differences in behavioral outcomes or lesion volumes after TBI as compared to wild-type controls. Using an in vitro reconstitution system, we also demonstrated that cleavage of DFF45 by caspase-3 is not sufficient for DNA fragmentation induced by protein extracts from rat brain cortex. We found that endonuclease activity induced in rat brain cortex following TBI depends on the presence of Mg2+ and Ca2+, but is not inhibited by Zn2+. Primary neuronal cultures from DFF45 knockouts failed to show DNA laddering in response to staurosporine, but did show prominent, albeit delayed, DNA fragmentation following treatment with etoposide. In contrast, primary neurons from wild-type animals demonstrated marked DNA fragmentation following treatment with staurosporine or etoposide. CONCLUSIONS: The results of this study suggest that, in addition to DFF45/40, other endonucleases may be essential for chromatin degradation during neuronal apoptosis in adult brain after TBI.     

Platelet-rich plasma-derived scaffolds increase the benefit of delayed mesenchymal stromal cell therapy after severe traumatic brain injury

Background

Cell therapy using mesenchymal stromal cells (MSCs) offers new perspectives in the treatment of traumatic brain injury (TBI). The aim of the present study was to assess the impact of platelet-rich plasma scaffolds (PRPS) as support of MSCs in a delayed phase after severe TBI in rats.