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Biomedical subjects

Patrick M Kochanek

Publications and source records attributed to Patrick M Kochanek.

At least 37 records · Page 2Linked to original sources
PubMed2006

Heme oxygenase 1 in cerebrospinal fluid from infants and children after severe traumatic brain injury.

Heme oxygenase 1 (HO-1) is an enzyme important in the catabolism of heme that is induced under conditions of oxidative stress. HO-1 degradation of heme yields biliverdin, bilirubin, carbon monoxide and iron. HO-1 is thought to serve a protective antioxidant function, and upregulation of HO-1 has been demonstrated in experimental models of neurodegeneration, subarachnoid hemorrhage, cerebral ischemia and traumatic brain injury (TBI). We measured HO-1 concentration in cerebral spinal fluid samples from 48 infants and children following TBI and 7 control patients by ELISA. Increased HO-1 was seen in TBI versus control patients--mean 2.75+/-0.63, peak 4.17+/-0.96 ng/ml versus control (<0.078 ng/ml, not detectable) (p<0.001). Increased HO-1 concentration was associated with increased injury severity and unfavorable neurological outcome (both p<0.05). Increased HO-1 concentration was independently associated with younger age; however, statistical analysis could not rule out the possibility that the effect of age was related to inflicted TBI from child abuse. HO-1 increases after TBI and appears to be more prominent in infants compared with older children after injury.

Age Factors↗
PubMed2006

Oxidative stress in immature brain after traumatic brain injury.

High oxygen demand along with the abundance of readily oxidizable substrates yielding productive oxidative metabolism are required for the normal function of the brain. This necessitates the existence of the complex and multicomponent antioxidant system in the brain for protection against oxidative damage. However, during development, individual components of the antioxidant system are not equally expressed and not always sufficient to fulfill their tasks in a coordinated way. As a result, the developing brain may be more vulnerable to oxidative insults than the adult brain. Traumatic brain injury is one of the damaging acute impacts that challenge the brain antioxidant reserves by exposing them to a number of decompartmentalized prooxidant molecules. This review focuses on the sources and assessment of oxidative stress and the link between oxidative stress and cell death pathways in the immature brain after experimental and clinical traumatic brain injury.

Animals↗
PubMed2006

Identification of inflicted traumatic brain injury in well-appearing infants using serum and cerebrospinal markers: a possible screening tool.

OBJECTIVE: Inflicted traumatic brain injury (iTBI) is the leading cause of death from TBI in infants. Misdiagnosis of iTBI is common and results in increased morbidity and mortality. Biomarkers may be able to assist in screening infants who are at high risk for iTBI and whose injury might otherwise be missed. We investigated whether serum and/or cerebrospinal fluid (CSF) concentrations of neuron-specific enolase (NSE), S100B, and myelin-basic protein (MBP) are sensitive and specific for iTBI in high-risk infants. METHODS: A prospective case-control study was conducted of 98 well-appearing infants who presented with nonspecific symptoms and no history of trauma. Serum or CSF was collected. NSE, S100B, and MBP concentrations were measured by enzyme-linked immunosorbent assay. Abnormal marker concentrations were defined a priori. Patients were followed for 12 months to assess for subsequent abuse. RESULTS: Fourteen patients received a clinical diagnosis of iTBI. Using preestablished cutoffs, NSE was 77% sensitive and 66% specific and MBP was 36% sensitive and 100% specific for iTBI. S100B was neither sensitive nor specific for iTBI. Five patients who were not identified with iTBI at enrollment were identified at follow-up as being possible victims of abuse; 4 had an increased NSE concentration at enrollment. CONCLUSIONS: Serum and/or CSF concentrations of NSE and MBP may be useful as a screening test to identify infants who are at increased risk for iTBI and may benefit from additional evaluation with a head computed tomography scan. S100B is neither sensitive nor specific for iTBI in this study population. The ability to identify iTBI that might otherwise be missed has important implications for decreasing the morbidity and the mortality from iTBI.

Biomarkers↗
PubMed2005

Increased phosphorylation of protein kinase B and related substrates after traumatic brain injury in humans and rats.

Activation of protein kinase B (PKB, also known as Akt) by phosphorylation at serine-473 and threonine-308 promotes cell survival in multiple in vitro and in vivo models where neuronal death is seen, including traumatic brain injury (TBI); however, whether PKB is activated in humans after TBI was heretofore unknown. Activated PKB inhibits apoptogenic factors and is involved in the regulation of several transcription factors. Accordingly, we examined phosphorylation of the PKB signaling pathway in humans as well as rats after TBI using phosphospecific antibodies. Increased phosphorylation of PKB and PKB substrates was detected in injured brain from both humans and rats. In humans, increased phosphorylation of the PKB signaling pathway-related proteins Bad and forkhead transcription factor (FKHR) was detected in patients with TBI versus controls. In rats, increased phosphorylation of FKHR, inhibitor of kappaBalpha, and cyclic adenosine monophosphate responsive element binding protein (CREB) was detected after TBI versus controls. The deoxyribonucleic acid-binding activity of CREB was also enhanced after TBI in rats. Increased phosphorylation of PKB and PKB substrates was identified in neurons and other cell types by immunohistochemistry in both humans and rats. These data show increased phosphorylation of PKB, PKB substrates, and related proteins after both experimental and clinical TBI, suggesting either activation of the PKB signaling pathway or reduced phosphatase activity in both species.

Adult↗
PubMed2005

Murine orthostatic response during prolonged vertical studies: effect on cerebral blood flow measured by arterial spin-labeled MRI.

High-field MRI scanners are, in principle, well suited for mouse studies; however, many high-field magnets employ a vertical design that may influence the physiological state of the rodent. The purpose of this study was to investigate the orthostatic response of cerebral blood flow (CBF) in mice during a prolonged MR experiment in the vertical position. Arterial spin-labeled (ASL) MRI was performed at 4.7-Tesla with a 15-cm gradient insert that allowed horizontal and vertical CBF measurements to be obtained with the same scanner. For mice in the head-up (HU) vertical position, CBF decreased by approximately 40% compared to the horizontal position, although blood pressure did not differ. Furthermore, CBF values for vertically positioned mice treated with phenylephrine remained constant while blood pressure increased. These results support the conclusion that cerebral autoregulation was intact, albeit at a lower level. Since CBF recovers to near horizontal values by volume loading with saline, it appears that a decrease in central venous pressure (CVP) leading to an increase in sympathetic tone may be a contributing mechanism for lowered CBF. This suggests that using an HU vertical position for MRI in mice may have broader implications, especially for studies that rely on CBF (such as BOLD and fMRI).

Adaptation, Physiological↗
PubMed2005

Pediatric traumatic brain injury: beyond the guidelines.

In 2003, a multidisciplinary group of physicians formulated the first guidelines for the management of severe traumatic brain injury in infants and children. Initial treatment of these patients is focused on stabilization to prevent the occurrence of secondary insults such as hypotension and hypoxemia. However, this article focuses on the established and emerging therapies used in the intensive care unit management of intracranial hypertension--which represents the key target for contemporary therapy of this condition. A critical pathway for the treatment of this condition was established within the guidelines, and this pathway is appropriately focused on limiting intracranial hypertension and optimizing cerebral perfusion during the intensive care unit phase. This includes first- and second-tier therapies. This article contains a brief synopsis of this critical pathway and discusses important new developments for the management of this condition. Key new developments include a better understanding of the optimal cerebral perfusion pressure target for intracranial pressure-directed therapy, with emerging evidence supporting the use of two therapeutic modalities, mild-moderate hypothermia and decompressive craniectomy.

Journal Article↗
PubMed2005

Enhanced oxidative stress in iNOS-deficient mice after traumatic brain injury: support for a neuroprotective role of iNOS.

Studies in experimental traumatic brain injury (TBI) suggest both deleterious and protective effects of inducible nitric oxide synthase (iNOS). Early after injury, iNOS may be detrimental via formation of peroxynitrite and iNOS inhibitors are protective. In contrast, we reported impaired long-term functional outcome after TBI in iNOS knockout (ko) versus wild-type (wt) mice. To elucidate potential neuroprotective and neurotoxic mechanisms for iNOS, we studied nitric oxide formation by electron paramagnetic resonance (EPR) spectroscopy using diethyldithiocarbamate-iron (DETC-Fe) as a spin trap and markers of nitrosative (S-nitrosothiol (RSNO, Fluorescent assay); nitrotyrosine (3NT, ELISA)) and oxidative stress (ascorbate, HPLC) at 72 h after controlled cortical impact (CCI) in iNOS ko and wt and in uninjured iNOS ko and wt mice. 3NT immunostaining with macrophage and myeloperoxidase (MPO) dual labeling was also assessed in brain sections. Brain DETC-Fe-NO low-temperature EPR signal intensity was approximately 2-fold greater in wt versus iNOS ko at 72 h after CCI. Ascorbate levels decreased in injured hemisphere in wt and iNOS ko versus uninjured -this decrease was more pronounced in iNOS ko. In wt mice, RSNO and 3NT levels were increased after CCI versus uninjured (50% and 400%, respectively, P < 0.05). RSNO levels were not increased in iNOS ko after CCI. Nitrotyrosine levels increased after CCI in wt and ko versus respective uninjured -this increase was more pronounced in wt (2.34 +/- 0.95 versus 1.27 +/- 0.49 pmol/mg protein, P < 0.05). Increased 3NT immunoreactivity was detected in wt versus iNOS ko at 72 h after CCI, and colocalized with macrophage marker and MPO. Our data support a role for iNOS-derived NO as an endogenous antioxidant after CCI. iNOS also contributes protein nitrosylation and nitration. Colocalization of 3NT with macrophages and MPO suggests generation of nitrating agents by macrophages and/or phagocytosis of nitrated proteins.

Animals↗
PubMed2005

Cytochrome c, a biomarker of apoptosis, is increased in cerebrospinal fluid from infants with inflicted brain injury from child abuse.

Previous studies suggest that delayed neuronal death occurs in patients with inflicted traumatic brain injury (TBI) from child abuse. It is unknown whether the mode of this delayed neuronal death represents apoptosis or necrosis, a distinction that carries therapeutic ramifications. Cytochrome c, an electron transport chain component, can be released from mitochondria under conditions of cellular stress, whereupon it can initiate and serve as a biomarker of apoptosis. To resolve this issue, cytochrome c concentration was determined in 167 ventricular cerebrospinal fluid (CSF) samples from 67 infants and children with TBI (including 15 patients diagnosed with child abuse) by ELISA. Controls included lumbar CSF from 19 infants and children without trauma or meningitis. A multivariate model adjusted for multiple within-subject observations was used to identify clinical variables associated with CSF cytochrome c. Other apoptosis-related proteins were also examined in a subset of TBI patients. Increased CSF cytochrome c was independently associated with inflicted TBI (P=0.0001) and female gender (P=0.04), but not age, Glasgow coma scale score, or survival. Other apoptosis-related proteins including Fas and caspase-1 were increased in CSF after TBI, but did not independently discriminate between accidental and inflicted TBI. These data suggest that apoptosis, as detected by the presence of cytochrome c in CSF, is uniquely prominent among the subset of TBI patients diagnosed with child abuse. The degree of apoptosis after TBI also appears to be gender-dependent. Development of strategies targeting apoptosis after TBI, particularly in victims of child abuse and in girls, appears justified.

Apoptosis↗
PubMed2005

Characterization of the effects of adenosine receptor agonists on cerebral blood flow in uninjured and traumatically injured rat brain using continuous arterial spin-labeled magnetic resonance imaging.

Hypoperfusion after traumatic brain injury may exacerbate damage. Adenosine, a vasodilator, regulates cerebral blood flow (CBF). Treatment with adenosine receptor agonists has shown benefit in experimental CNS trauma; however, their effects on CBF after injury remain undefined. We used magnetic resonance imaging to assess CBF in uninjured rats both early and at 24 h after intrahippocampal administration of either the nonselective adenosine receptor agonist 2-chloroadenosine (2-CA, 12 nmol) or the A(2A)-receptor agonist 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarbox-amidoadenosine (CGS 21680, 6 nmol). We also assessed the effects of these agents on cerebral metabolic rate for glucose (CMRglu). We then assessed the effect of 2-CA on CBF at 3.5 to 5 h after controlled cortical impact (CCI). Injection of 2-CA into uninjured rat brain produced marked increases in CBF in ipsilateral hippocampus and cortex versus vehicle (P<0.05); CBF increases persisted even at 24 h. Measurement of hippocampal levels of 2-CA showed persistent increases to 24 h. CGS 21680 produced even more marked global increases in CBF than seen with 2-CA (2-6-fold versus vehicle, P<0.05 in 10/12 regions of interest (ROIs)). Neither agonist altered CMRglu versus vehicle. After CCI, 2-CA increased CBF in ipsilateral hippocampal and hemispheric ROIs (P<0.05 versus vehicle), but the response was attenuated at severe injury levels. We report marked increases in CBF after injection of adenosine receptor agonists into uninjured rat brain despite unaltered CMRglu. 2-Chloroadenosine produced enduring increases in CBF in uninjured brain and attenuated posttraumatic hypoperfusion. Future studies of adenosine-related therapies in CNS injury should address the role of CBF.

2-Chloroadenosine↗
PubMed2005

Mild hypothermia improves survival after prolonged, traumatic hemorrhagic shock in pigs.

INTRODUCTION: Clinical studies have demonstrated improved survival after cardiac arrest with induction of mild hypothermia (34 degrees C). Infusion of ice-cold saline seems beneficial. The American Heart Association recommends therapeutic hypothermia for comatose survivors of cardiac arrest. For hemorrhagic shock (HS), laboratory studies suggest that mild hypothermia prolongs the golden hour for resuscitation. Yet, the effects of hypothermia during HS are unclear since retrospective clinical studies suggest that hypothermia is associated with increased mortality. Using a clinically relevant, large animal model with trauma and intensive care, we tested the hypothesis that mild hypothermia, induced with intravenous cold saline (ice cold or room temperature) and surface cooling, would improve survival after HS in pigs. METHODS: Pigs were prepared under isoflurane anesthesia. After laparotomy, venous blood (75 mL/kg) was continuously withdrawn over 3 hours (no systemic heparin). At HS 35 minutes, the spleen was transected. At HS 40 minutes, pigs were divided into three groups (n = 8, each): 1) Normothermia (Norm)(38 degrees C), induced with warmed saline; 2) Mild hypothermia (34 degrees C) induced with i.v. infusion of 2 degrees C saline (Hypo-Ice) and surface cooling; and 3) Mild hypothermia (34 degrees C), induced with room temperature (24 degrees C) i.v. saline (Hypo-Rm) and surface cooling. Fluids were given when mean arterial pressure (MAP) was <30 mmHg. At HS 3 hours, shed blood was returned and splenectomy was performed. Intensive care was continued to 24 hours. RESULTS: At 24 hours, there were two survivors in the Norm group, four in the Hypo-Ice group and seven in the Hypo-Rm group (p < 0.05 versus the Norm group, Log Rank). Time required to achieve 34 degrees C was 17 +/- 9 minutes in the Hypo-Ice group and 15 +/- 4 minutes in the Hypo-Rm group (NS). Compared with the Hypo-Rm group, the Hypo-Ice group required less saline during early HS (321 +/- 122 versus 571 +/- 184 mL, p < 0.05). The Hypo-Ice group also had higher lactate levels than the Hypo-Rm group (p < 0.05). Hypothermia did not cause any increase in bleeding compared with normothermia. CONCLUSION: Mild hypothermia during HS, induced by infusion of room temperature saline and surface cooling, improves survival in a clinically relevant model of HS and trauma. However, the use of iced saline in this model had detrimental effects and did not cool the animal more quickly than room temperature fluids. These findings suggest that optimal methods for induction of hypothermia need to be addressed for each potential indication, e.g. cardiac arrest versus HS.

Animals↗
PubMed2005

Serum neuron-specific enolase, S100B, and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children.

OBJECT: Misdiagnosis of inflicted traumatic brain injury (iTBI) is common. Serum biomarkers may be able to assist in the detection of iTBIs that would otherwise be missed. The authors investigated whether serum concentrations of biomarkers were increased after noninflicted (n)TBI and iTBI in pediatric cases of varying severity. METHODS: This prospective, case-control study involved 100 patients (56 with nTBI, 44 with iTBI) and 64 controls. Blood was collected in patients within 12 hours of injury; a subset had serial samples. A single sample was collected from controls. Serum neuron-specific enolase (NSE), S100B, and myelin basic protein concentrations were measured. Abnormal concentrations were defined using receiver-operator characteristic (ROC) curves. The sensitivity and specificity of initial NSE and S100B and peak myelin basic protein concentrations for identifying TBI at ROC curve-defined cutoffs were 71 and 64% (NSE), 77 and 72% (S100B), and 44 and 96% (myelin basic protein), respectively. Eighty-six percent of patients having suffered iTBI had one or more biomarkers increased, including 82% of children with iTBI and a Glasgow Coma Scale score of 15, and two children with iTBI who were initially misdiagnosed. Children with iTBI had a later peak concentration of all three biomarkers and were more likely to have increased myelin basic protein levels at admission compared with patients with nTBI. CONCLUSIONS: Serum NSE, S100B, or myelin basic protein are increased in the majority of children with acute nTBI and iTBI, including well-appearing children with iTBI in whom the diagnosis might otherwise have been missed. Differences in the time course of NSE, S100B, and myelin basic protein after nTBI and iTBI may provide insight into the pathophysiology of iTBI. These serum markers should be prospectively evaluated in a target population of infants.

Biomarkers↗
PubMed2004

Bench-to-bedside review: Apoptosis/programmed cell death triggered by traumatic brain injury.

Apoptosis, or programmed cell death, is a physiological form of cell death that is important for normal embryologic development and cell turnover in adult organisms. Cumulative evidence suggests that apoptosis can also be triggered in tissues without a high rate of cell turnover, including those within the central nervous system (CNS). In fact, a crucial role for apoptosis in delayed neuronal loss after both acute and chronic CNS injury is emerging. In the current review we summarize the growing evidence that apoptosis occurs after traumatic brain injury (TBI), from experimental models to humans. This includes the identification of apoptosis after TBI, initiators of apoptosis, key modulators of apoptosis such as the Bcl-2 family, key executioners of apoptosis such as the caspase family, final pathways of apoptosis, and potential therapeutic interventions for blocking neuronal apoptosis after TBI.

Animals↗
PubMed2004

Innate gender-based proclivity in response to cytotoxicity and programmed cell death pathway.

Many central nervous system (CNS) diseases display sexual dimorphism. Exposure to circulating sex steroids is felt to be a chief contributor to this phenomenon; however, CNS diseases of childhood and the elderly also demonstrate gender predominance and/or a sexually dimorphic response to therapies. Here we show that XY and XX neurons cultured separately are differentially susceptible to various cytotoxic agents and treatments. XY neurons were more sensitive to nitrosative stress and excitotoxicity versus XX neurons. In contrast, XX neurons were more sensitive to etoposide- and staurosporine-induced apoptosis versus XY neurons. The responses to specific therapies were also sexually dimorphic. Moreover, gender proclivity in programmed cell death pathway was observed. After cytotoxic challenge, programmed cell death proceeded predominately via an apoptosis-inducing factor-dependent pathway in XY neurons versus a cytochrome c-dependent pathway in XX neurons. This gender-dependent susceptibility is related to the incapacity of XY neurons to maintain intracellular levels of reduced glutathione. In vivo studies further demonstrated an incapacity for male, but not female, 17-day-old rats to maintain reduced glutathione levels within cerebral cortex acutely after an 8-min asphyxial cardiac arrest. This gender difference in sensitivity to cytotoxic agents may be generalized to nonneuronal cells, as splenocytes from male and female 16-18-day-old rats show similar gender-dependent responses to nitrosative stress and staurosporine-induced apoptosis. These data support gender stratification in the evaluation of mechanisms and treatment of CNS disease, particularly those where glutathione may play a role in detoxification, such as Parkinson's disease, traumatic brain injury, and conditions producing cerebral ischemia, and may apply to non-CNS diseases as well.

Animals↗
PubMed2004

Biochemical markers of brain injury: could they be used as diagnostic adjuncts in cases of inflicted traumatic brain injury?

Child abuse is the leading cause of serious traumatic brain injury (TBI) in infants and young children (Billmire & Myers, 1985; Bruce & Zimmerman, 1989). The incidence of serious or fatal inflicted traumatic brain injury (iTBI) in children < 1 year of age is approximately 1 in 3,300 ( Keenan et al., 2003); since many cases of iTBI are of mild or moderate severity, the incidence is probably significantly higher. Even at an incidence of 1 in 3,300, iTBI is as common as the incidence of cystic fibrosis (CF), the most common genetic recessive disease in the Caucasian population. Proper diagnosis of iTBI is difficult even for experienced and astute physicians because its presentation can be subtle and important historical data are often lacking. As a result, misdiagnosis is common and can have catastrophic medical consequences for patients and significant financial consequences for society ( Ewing-Cobbs et al., 1998; Jenny, Hymel, Pitzen, Reinert, & Hay, 1999). Unlike CF for which there are several well established screening tests, there are currently no diagnostic adjuncts to help physicians screen for possible iTBI.

Adolescent↗
PubMed2004

Relationships between cerebrospinal fluid markers of excitotoxicity, ischemia, and oxidative damage after severe TBI: the impact of gender, age, and hypothermia.

Excitotoxicity and ischemia can result in oxidative stress after TBI. Female sex hormones are hypothesized to be neuroprotective after TBI by affecting multiple mechanisms of secondary injury, including oxidative damage, excitotoxicity and ischemia. Ca2+ mediated oxidative stress increases with age, and hypothermia is known to attenuate secondary injury. The purpose of this study was to determine if the relationship between cerebral spinal fluid (CSF) markers of excitotoxicity, ischemia, and oxidative damage are gender and age specific and the role of hypothermia in affecting these relationships. F2-isoprostane, glutamate, and lactate/pyruvate, were assessed in CSF from adults (n = 68) with severe TBI (Glasgow coma scale [GCS] score </= 8) using ventricular CSF samples (n = 207) collected on days 1, 2, and 3 post-injury. F2-isoprostane/glutamate and F2-isoprostane/lactate/pyruvate ratios were determined for patients at each time point. Six-month Glasgow Outcome Scores (GOS) were also obtained. Repeated measures multivariate analysis showed a significant gender effect (p < 0.002) and gender*time interaction (p = 0.012) on F2-isoprostane/glutamate ratios. A significant gender effect (p = 0.050) and gender*time interaction (p = 0.049) was also seen with F2-isoprostane/lactate/pyruvate. Hypothermia (p = 0.001) and age (p = 0.026) significantly increased F2-isoprostane/glutamate ratios. Females had a significant inverse relationship between day 1 F2-isoprostane/glutamate ratios and GOS scores (r =- 0.43; p = 0.05) as well as day 1 F2-isoprostane/lactate/pyruvate ratio (r =- 0.46; p = 0.04) and GOS scores. These results indicate that females have smaller oxidative damage loads than males for a given excitotoxic or ischemic insult and female gonadal hormones may play a role in mediating this neuroprotective effect. These results also suggest that susceptibility to glutamate mediated oxidative damage increases with age and that hypothermia differentially attenuates CSF glutamate versus F2-isoprostane production. Gender and age differences in TBI pathophysiology should be considered when conducting clinical trials in TBI.

Adult↗
PubMed2004

Induction of the stress response after inflicted and non-inflicted traumatic brain injury in infants and children.

Rapid induction of 72-kD heat shock protein (Hsp70) is a key component of the stress response and is seen after a variety of insults to the brain including experimental hyperthermia, ischemia, seizures, and traumatic brain injury (TBI). Little is known about the endogenous stress response in pediatric patients after brain injury. Accordingly, the concentration of Hsp70 was determined in 61 cerebrospinal fluid (CSF) samples from 20 infants and children after TBI. Peak Hsp70 level were increased in TBI patients vs. controls (4.60 [1.49-78.99] vs. 2.18 [1.38-4.25] ng/mL, respectively, median (range), p = 0.01) and occurred most often on day 1 after injury. Strikingly, CSF levels of Hsp70 were positively and independently associated with inflicted vs. non-inflicted TBI (7.03 [2.30-27.22] vs. 2.06 [1.06-78.99] ng/mL, respectively, p = 0.05). Endogenous Hsp70 expression was confirmed by Western blot and immunocytochemistry using brain tissue samples removed from patients who underwent decompressive craniotomy for refractory intracranial hypertension or at autopsy. These data suggest that the endogenous stress response, as measured and quantified by the Hsp70 concentration in CSF, occurs in infants and children after TBI. The endogenous stress response is more robust in victims of child abuse, compared with patients with accidental TBI, supporting age-dependence or a difference in either injury frequency, duration, severity, or mechanism in this subgroup of TBI patients. Further studies are needed to determine the role of Hsp70 in both non-inflicted and inflicted TBI in infants and children.

Accidents↗