PubMed Health⌕ Search

Biomedical subjects

C Edward Dixon

Publications and source records attributed to C Edward Dixon.

At least 19 recordsLinked to original sources
PubMed2006

Delayed increase of tyrosine hydroxylase expression in rat nigrostriatal system after traumatic brain injury.

Tyrosine hydroxylase (TH) is the key enzyme for synthesizing dopamine (DA) in dopaminergic neurons and its terminals. Emerging experimental and clinical evidence support the hypothesis of a disturbance in dopamine neurotransmission following traumatic brain injury (TBI). However, the effect of controlled cortical impact (CCI) injury on TH in the nigrostriatal system is currently unknown. To determine if there is an alteration in TH after CCI injury, we examined TH levels at 1 day, 7 days, and 28 days post-injury by utilizing a commercially available antibody specific to TH. Rats were anesthetized and surgically prepared for CCI injury (4 m/s, 3.2 mm) or sham surgery. Injured (N=6) and sham animals (N=6) were sacrificed and coronally sectioned (35 microm thick) through the striatum and substantia nigra (SN) for immunohistochemistry. Additionally, semiquantitative measurements of TH protein in striatal and SN homogenates from injured (N=6) and sham (N=6) rats sacrificed at the appropriate time post-surgery were assessed using Western blot analysis. TH protein is bilaterally increased at 28 days post-injury in nigrostriatal system revealed by immunohistochemistry in injured rats compared to sham controls. Western blot analysis confirms the findings of immunohistochemistry in both striatum and SN. We speculate that the increase in TH in the nigrostriatal system may reflect a compensatory response of dopaminergic neurons to upregulate their synthesizing capacity and a delayed increase in the efficiency of DA neurotransmission after TBI.

Animals↗
PubMed2006

Transgenic mice that overexpress the anti-apoptotic Bcl-2 protein have improved histological outcome but unchanged behavioral outcome after traumatic brain injury.

Increasing evidence suggests that apoptosis is a contributing factor to neuronal cell death in traumatic brain injury (TBI). There is increased expression, cleavage and activation of caspases as well as other proteins known to regulate apoptosis in neurons after TBI. These proteins include the proto-oncogene Bcl-2 which belongs to a family of proteins with both pro- and anti-apoptotic properties. To investigate the role of apoptosis in TBI and the importance of Bcl-2 protein on the severity and outcome of injury, Bcl-2 overexpressing transgenic and wild-type control mice were subjected to the controlled cortical impact model of TBI. There was no significant difference in the cleavage of caspase-3 or caspase-9 detected by Western blotting of hippocampal samples from transgenic or wild-type mice after TBI. Bcl-2 transgenic mice had smaller contusion volumes and increased numbers of surviving neurons in CA2 but not other regions of hippocampus compared to wild-type controls. By contrast, there was no difference in motor function determined by the round beam balance and wire grip tests between transgenic and wild-type mice after TBI. Cognitive function assessed by the Morris water maze was also not different between groups. These results suggest that overexpression of Bcl-2 is only partially neuroprotective and other members of this protein family may prove to be more important in protecting neurons from cell death.

Animals↗
PubMed2006

boc-Aspartyl(OMe)-fluoromethylketone attenuates mitochondrial release of cytochrome c and delays brain tissue loss after traumatic brain injury in rats.

The pathobiology of traumatic brain injury (TBI) includes activation of multiple caspases followed by cell death with a spectrum of apoptotic phenotypes. There are initiator (e.g. caspase-2, -8, and -9) and effector (e.g. caspase-3 and -7) caspases. Recently, caspase-2 and -8 have been shown to regulate cell death via provoking cytochrome c release from the mitochondria upstream of caspase-9. Here, we show that an intracerebral injection of the pan-caspase inhibitor boc-Aspartyl(OMe)-fluoromethylketone (BAF; 1 micromol) 1 min after TBI in rats reduces caspase-3-like activity, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and tissue damage, and cytochrome c release in ipsilateral cortex at 24 h versus vehicle. To investigate whether either caspase-2 and/or caspase-8 activation may contribute to cytochrome release, the effect of BAF treatment on caspase-2 and caspase-8 proteolysis was also examined. boc-aspartyl(OMe)-fluoromethylketone treatment inhibited proteolysis of caspase-2 but not caspase-8 24 h after TBI in rats versus vehicle. However, BAF with or without nerve growth factor (12.5 ng/h x 14 days intracerebrally via osmotic pump) did not result in differences in motor function, Morris water maze performance, hippocampal neuron survival, nor contusion volume at 14 days. These data suggest that BAF treatment reduces acute cell death after TBI by inhibiting mitochondrial release of cytochrome c, possibly via a mechanism involving initiator caspases; however, BAF appears to delay cell death, rather than result in permanent protection.

Amino Acid Chloromethyl Ketones↗
PubMed2006

Isoflurane exerts neuroprotective actions at or near the time of severe traumatic brain injury.

Isoflurane improves outcome vs. fentanyl anesthesia, in experimental traumatic brain injury (TBI). We assessed the temporal profile of isoflurane neuroprotection and tested whether isoflurane confers benefit at the time of TBI. Adult, male rats were randomized to isoflurane (1%) or fentanyl (10 mcg/kg iv bolus then 50 mcg/kg/h) for 30 min pre-TBI. Anesthesia was discontinued, rats recovered to tail pinch, and TBI was delivered by controlled cortical impact. Immediately post-TBI, rats were randomized to 1 h of isoflurane, fentanyl, or no additional anesthesia, creating 6 anesthetic groups (isoflurane:isoflurane, isoflurane:fentanyl, isoflurane:none, fentanyl:isoflurane, fentanyl:fentanyl, fentanyl:none). Beam balance, beam walking, and Morris water maze (MWM) performances were assessed over post-trauma d1-20. Contusion volume and hippocampal survival were assessed on d21. Rats receiving isoflurane pre- and post-TBI exhibited better beam walking and MWM performances than rats treated with fentanyl pre- and any treatment post-TBI. All rats pretreated with isoflurane had better CA3 neuronal survival than rats receiving fentanyl pre- and post-TBI. In rats pretreated with fentanyl, post-traumatic isoflurane failed to affect function but improved CA3 neuronal survival vs. rats given fentanyl pre- and post-TBI. Post-traumatic isoflurane did not alter histopathological outcomes in rats pretreated with isoflurane. Rats receiving fentanyl pre- and post-TBI had the worst CA1 neuronal survival of all groups. Our data support isoflurane neuroprotection, even when used at the lowest feasible level before TBI (i.e., when discontinued with recovery to tail pinch immediately before injury). Investigators using isoflurane must consider its beneficial effects in the design and interpretation of experimental TBI research.

Anesthetics, Intravenous↗
PubMed2006

Immunohistochemical analysis of histone H3 acetylation and methylation--evidence for altered epigenetic signaling following traumatic brain injury in immature rats.

Posttranslational modifications (PTMs) of histone proteins may result in altered epigenetic signaling after pediatric traumatic brain injury (TBI). Hippocampal histone H3 acetylation and methylation in immature rats after moderate TBI were measured and decreased only in CA3 at 6 h and 24 h with persistent methylation decreases up to 72 h after injury. Decreased histone H3 acetylation and methylation suggest altered hippocampal CA3 epigenetic signaling during the first hours to days after TBI.

Acetylation↗
PubMed2006

Adenosine A1 receptor knockout mice develop lethal status epilepticus after experimental traumatic brain injury.

Adenosine, acting at A1 receptors, exhibits anticonvulsant effects in experimental epilepsy--and inhibits progression to status epilepticus (SE). Seizures after traumatic brain injury (TBI) may contribute to pathophysiology. Thus, we hypothesized that endogenous adenosine, acting via A1 receptors, mediates antiepileptic benefit after experimental TBI. We subjected A1-receptor knockout (ko) mice, heterozygotes, and wild-type (wt) littermates (n=115) to controlled cortical impact (CCI). We used four outcome protocols in male mice: (1) observation for seizures, SE, and mortality in the initial 2 h, (2) assessment of seizure score (electroencephalogram (EEG)) in the initial 2 h, (3) assessment of mortality at 24 h across injury levels, and (4) serial assessment of arterial blood pressure, heart rate, blood gases, and hematocrit. Lastly, to assess the influence of gender on this observation, we observed female mice for seizures, SE, and mortality in the initial 2 h. Seizure activity was noted in 83% of male ko mice in the initial 2 h, but was seen in no heterozygotes and only 33% of wt (P<0.05). Seizures in wt were brief (1 to 2 secs). In contrast, SE involving lethal sustained (>1 h) tonic clonic activity was uniquely seen in ko mice after CCI (50% incidence in males), (P<0.05). Seizure score was twofold higher in ko mice after CCI versus either heterozygote or wt (P<0.05). An injury-intensity dose-response for 24 h mortality was seen in ko mice (P<0.05). Physiologic parameters were similar between genotypes. Seizures were seen in 100% of female ko mice after CCI versus 14% of heterozygotes and 25% wt (P<0.05) and SE was restricted to the ko mice (83% incidence). Our data suggest a critical endogenous anticonvulsant action of adenosine at A1 receptors early after experimental TBI.

Animals↗
PubMed2006

Comparison of seven anesthetic agents on outcome after experimental traumatic brain injury in adult, male rats.

Isoflurane is commonly used in experimental traumatic brain injury (TBI), both before and early after injury, yet it is rarely used clinically. Narcotics and benzodiazepines are frequently used after injury in clinical TBI. We compared seven anesthetic/sedative agents applied after injury in the controlled cortical impact model: diazepam, fentanyl, isoflurane, ketamine, morphine, pentobarbital, and propofol. Our objective was to provide insight into the relative degrees of neuroprotection provided by these agents in a standard model of TBI. We hypothesized that the choice of anesthetic/sedative early after experimental TBI critically impacts outcome and that the agents most commonly used clinically may be less neuroprotective than isoflurane. Rats treated with isoflurane had the best cognitive recovery (p < 0.05) and hippocampal neuronal survival (p < 0.05). Conversely, rats treated with ketamine had the most hippocampal neuronal death (p < 0.05). Morphine or propofol, two agents commonly used clinically, were associated with the poorest motor function on post-trauma day 1-5 (p < 0.05). Our data support beneficial effects of isoflurane early after experimental TBI. Our data suggest that the early post-TBI use of isoflurane, despite practical logistical issues, could potentially provide clinical benefits in TBI--versus other commonly used sedatives or analgesics. Furthermore, the choice of post-injury sedation and analgesia could have important implications on attempts to translate novel therapies from bench to field or bedside.

Anesthetics↗
PubMed2006

Gel-based hippocampal proteomic analysis 2 weeks following traumatic brain injury to immature rats using controlled cortical impact.

Traumatic brain injury (TBI) to postnatal day 17 rats has been shown to produce acute changes in hippocampal global protein levels and spatial learning and memory deficits. The purpose of the present study was to analyze global hippocampal protein changes 2 weeks after a moderate ipsilateral controlled cortical impact in postnatal day 17 rats using 2-dimensional difference gel electrophoresis and mass spectrometry. Paired sham and ipsilateral injured hippocampal lysates were independently labeled with different fluorescent cyanine dyes and coseparated within the same immobilized pH gradient strips and slab gel based on isoelectric point and molecular mass. Significant changes in key proteins involved in glial and neuronal stress, oxidative metabolism, calcium uptake and neurotransmitter function were found 2 weeks after injury, and their potential roles in hippocampal plasticity and cognitive dysfunction were discussed.

Aging↗
PubMed2005

Synaptosomal dopamine uptake in rat striatum following controlled cortical impact.

Functional deficits following traumatic brain injury (TBI) are associated with alterations in markers of dopaminergic neurotransmission. To assess the effects of TBI on the expression and functional integrity of dopamine transporters, we measured transporter protein levels and investigated synaptosomal dopamine uptake in the rat striatum. Two or four weeks after lateral controlled cortical impact or sham injury, Western blotting revealed a decrease in transporter protein in the ipsilateral striatum of injured rats relative to shams (P < 0.05). However, no significant difference in synaptosomal uptake (K(m), V(max)) was found between injured and sham-injured animals. Our data suggest that striatal dopamine transporters are capable of normal function at 2 weeks and 4 weeks after injury. However, it is unclear whether neurons in the injured striatum can properly regulate the activity of dopamine transporters in vivo.

Adrenergic Agents↗
PubMed2005

Gender and environmental enrichment impact dopamine transporter expression after experimental traumatic brain injury.

Dopamine (DA) systems are implicated in cognitive deficits following traumatic brain injury (TBI). Rodent studies have demonstrated that both environmental enrichment (EE) and sex hormones can influence DA systems. The dopamine transporter (DAT) plays a crucial role in regulating DA transmission, and previous work shows that DAT is decreased after TBI in males. Therefore, the purpose of this study was to examine the effects of gender and EE on frontal cortex and striatal DAT expression after TBI. Sprague-Dawley male (n = 24) and cycling female rats (n = 24) were placed into EE or standard housing after controlled cortical impact (2.7 mm, 4.0 m/s) injury or sham surgery (eight groups, n = 6/group). Four weeks post-surgery, bilateral frontal cortex and striatal DAT expression was examined via Western blot. Results demonstrated that there was a significant effect of injury, EE, and region on DAT expression (P < 0.05 all comparisons) on female groups. There were no significant DAT decreases in any region as a result of injury, however, EE did promote significant post-injury DAT decreases in the striatum and ipsilateral frontal cortex (P < 0.05 all comparisons) compared to female shams housed in the standard environment. For males, there was a significant effect of injury, EE, and region for male groups (P < 0.05 all comparisons). There were decreases in DAT expression in three regions studied for injured males housed in the standard environment compared to sham males in the standard environment (P < 0.05 all comparisons), however, EE did not add significantly to post-injury DAT decreases in these regions. These results suggest that CCI causes larger relative decreases in DAT expression for males compared to females and that treatment with EE has larger effects on post-injury DAT expression for females than males. These findings may have some relevance to treatment paradigms using dopaminergic neurostimulants after TBI.

Analysis of Variance↗
PubMed2004

Time dependent alterations in dopamine tissue levels and metabolism after experimental traumatic brain injury in rats.

Several studies have demonstrated alterations in the dopamine (DA) system after traumatic brain injury (TBI). The present study investigated the temporal changes in DA tissue levels and metabolism at 1-h or 1, 7, 14, and 28 days after cortical impact or sham injury in rats. DA and DOPAC levels were measured by HPLC in the frontal cortex (FC) and striatum. DA levels were significantly increased at 1h in the contralateral FC and at 1 day in the ipsilateral FC versus respective sham groups. DA and DOPAC levels were significantly increased bilaterally at 1h in the striatum versus sham. These data indicate that TBI induces an early increase in DA and DOPAC, which returns to sham levels over time.

Animals↗
PubMed2004

Evaluation of estrous cycle stage and gender on behavioral outcome after experimental traumatic brain injury.

Female sex hormones are acutely neuroprotective in experimental models of traumatic brain injury (TBI). Because hormonal profiles are known to vary with estrous cycle stage, the purpose of this study was to evaluate how pre-injury estrous stage affects motor and cognitive performance after experimental TBI. We also sought to compare post-injury behavioral performance in males vs. females. Under anesthesia, male (n=18) and female (n=35) Sprague-Dawley rats underwent either controlled cortical impact (CCI) injury (2.7 mm; 4 m/s) or sham operations. Females were grouped according to estrous stage (proestrous or non-proestrous) at the time of surgery. Motor function was assessed pre-injury and for the first 5 days after surgery using beam balance and walking tasks. Spatial memory was assessed beginning 14 days post-injury utilizing the Morris water maze (MWM) task. No significant differences were found on any task between injured females regardless of estrous cycle stage. Females performed significantly better than males on both motor tasks, but gender did not influence MWM performance. Mixed effects multivariate analysis corroborated these results by showing that pre-injury serum hormone levels had little affect on behavioral performance. The results suggest that the presence of endogenous circulating hormones, rather than hormonal status at time of injury, may confer early neuroprotection in females after TBI. The impact of early neuroprotection on later behavioral outcome and the anatomic structural specificity of hormonal neuroprotection require further study.

Analysis of Variance↗
PubMed2004

The therapeutic efficacy conferred by the 5-HT(1A) receptor agonist 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) after experimental traumatic brain injury is not mediated by concomitant hypothermia.

We recently reported that the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) attenuated traumatic brain injury (TBI)-induced cognitive deficits and histopathology. However, 8-OH-DPAT also produced mild hypothermia (Hypo), which may have contributed to the benefit. To clarify this issue, we conducted an experiment similar to the previous, but included an 8-OH-DPAT group that was maintained at 37 +/- 0.5 degrees C (normothermia; Normo). Isoflurane-anesthetized rats received either a cortical impact (2.7-mm deformation at 4 m/sec) or sham injury and then were randomly assigned to two saline (Sham/Vehicle, n = 5; Injury/Vehicle, n = 10) or three 8-OH-DPAT (Sham/DPAT, n = 5; Injury/DPAT + Normo, n = 10; Injury/DPAT + Hypo, n = 10) groups. 8-OH-DPAT (0.5 mg/kg) or a comparable volume of saline was administered intraperitoneally 15 min after cortical impact or sham injury. Core temperatures were taken prior to treatment and every 15 min thereafter for 2 h. Function was assessed by established motor and cognitive tasks on post-operative days 1-5 and 14-20, respectively. Hippocampal CA1/CA3 cell survival and cortical lesion volume were quantified at 4 weeks. Both the Injury/DPAT + Normo and Injury/DPAT + Hypo groups exhibited enhanced cognitive performance (spatial acquisition and retention) and reduced histopathology (CA3 cell loss and cortical lesion volume) versus the Injury/ Vehicle group (P < 0.05), but did not differ from one another despite a rapid (15 min), mild (34.4-34.9 degrees C), and transient (~1 h) hypothermic effect in the latter. These data confirm that a single systemic administration of 8-OH-DPAT confers neurological protection after TBI, and demonstrate that the beneficial effect is not mediated by concomitant hypothermia. The mechanisms for the protective effects of 8-OH-DPAT after TBI require further inquiry.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2004

Time course analysis of hippocampal nerve growth factor and antioxidant enzyme activity following lateral controlled cortical impact brain injury in the rat.

Gradual secondary injury processes, including the release of toxic reactive oxygen species, are important components of the pathogenesis of traumatic brain injury (TBI). The extent of oxidative stress is determined in part by the effectiveness of the antioxidant response, involving the enzymes glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Since nerve growth factor (NGF) may be involved in the initiation of antioxidant activity, we employed a controlled cortical impact injury model in rats to produce secondary hippocampal damage and determined the subsequent time course of changes in NGF production and GPx, CAT, and SOD activity in this brain region. Hippocampal NGF production showed a rapid increase with a biphasic response after TBI. NGF protein was increased at 6 h, plateaued at 12 h, declined by 7 days, and exhibited a second rise at 14 days after injury. Similar to NGF, hippocampal GPx activity also showed a biphasic response, increasing by 12 h, declining at 24 h, and exhibiting a second peak at 7 days. In contrast, increased CAT activity occured steadily from 1 day through 7 days after injury. SOD activity was decreased at 6 h after injury, and continued to decline through 14 days. The initial rise in NGF preceded that of CAT, and coincided with an increase in GPX and a drop in SOD activity. These data demonstrate a complex temporal spectrum of antioxidant enzyme activation following secondary brain injury in the hippocampus, and suggest a selective regulatory role for NGF in this response.

Animals↗
PubMed2004

Bromocriptine reduces lipid peroxidation and enhances spatial learning and hippocampal neuron survival in a rodent model of focal brain trauma.

Oxidative stress is a significant contributor to the secondary sequelae of traumatic brain injury (TBI), and may mediate subsequent neurobehavioral deficits and histopathology. The present study examined the neuroprotective effects of bromocriptine (BRO), a dopamine D2 receptor agonist with significant antioxidant properties, on cognition, histopathology, and lipid peroxidation in a rodent model of focal brain trauma. BRO (5 mg/kg) or a comparable volume of vehicle (VEH) was administered intraperitoneally 15 min prior to cortical impact or sham injury. In experiment 1, spatial learning was assessed in an established water maze task on post-surgery days 14-18, followed by quantification of hippocampal cell survival and cortical lesion volume at 4 weeks. In experiment 2, rats were sacrificed 1 hr post-surgery, and malondialdehyde (MDA), the end product of lipid peroxidation, was measured in the frontal cortex, striatum, and substantia nigra using a thiobarbituric acid reactive substances assay. The TBI+BRO group was significantly more adept at locating a hidden platform in the water maze compared to the TBI+VEH group and also exhibited a greater percentage of surviving CA3 hippocampal neurons. TBI increased MDA in all examined regions of the VEH-treated, but not BRO-treated group versus SHAMs. MDA was significantly decreased in both the striatum (4.22 +/- 0.52 versus 5.60 +/- 0.44 nmol per mg/tissue +/- SEM) and substantia nigra (4.18 +/- 0.35 versus 7.76 +/- 2.05) of the TBI+BRO versus TBI+VEH groups, respectively, while only a trend toward decreased MDA was observed in the frontal cortex (5.44 +/- 0.44 versus 6.96 +/- 0.77). These findings suggest that TBI-induced oxidative stress is attenuated by acute BRO treatment, which may, in part, explain the benefit in cognitive and histological outcome.

Animals↗
PubMed2004

Experimental model of pediatric asphyxial cardiopulmonary arrest in rats.

OBJECTIVE: Develop a clinically relevant model of pediatric asphyxial cardiopulmonary arrest in rats. DESIGN: Prospective interventional study. SETTING: University research laboratory. SUBJECTS: Postnatal day 16-18 rats (n = 9/group). INTERVENTIONS: Anesthetized rats were endotracheally intubated and mechanically ventilated, and vascular catheters were inserted. Vecuronium was administered, and the ventilator was disconnected from the rats for 8 mins, whereupon rats were resuscitated with epinephrine, sodium bicarbonate, and chest compressions until spontaneous circulation returned. Shams underwent all procedures except asphyxia. MEASUREMENTS AND MAIN RESULTS: Asphyxial arrest typically occurred by 1 min after the ventilator was disconnected. Return of spontaneous circulation typically occurred <30 secs after resuscitation. An isoelectric electroencephalograph was observed for 30 mins after asphyxia, and rats remained comatose for 12-24 hrs. Overall survival rate was 85%. Motor function measured using beam balance and inclined plane tests was impaired on days 1 and 2, but recovered by day 3, in rats after asphyxia vs. sham injury (p <.05). Spatial memory acquisition measured using the Morris-water maze on days 7-14 and 28-35 was also impaired in rats after asphyxia vs. sham injury (total latency 379 +/- 28 vs. 501 +/- 40 secs, respectively, p <.05). DNA fragmentation was detected in CA1 hippocampal neurons bilaterally 3-7 days after asphyxia. Neurodegeneration detected using Fluorojade B was seen in bilateral CA1 hippocampi and layer V cortical neurons 3-7 days after asphyxia, with persistent neurodegeneration in CA1 hippocampus detected up to 5 wks after asphyxia. CA1 hippocampal neuron survival after asphyxia was 39-43% (p <.001 vs. sham). Evidence of DNA or cellular injury was not detected in sham rats. CONCLUSIONS: This model of asphyxial cardiopulmonary arrest in postnatal day 17 rats produces many of the clinical manifestations of pediatric hypoxic-ischemic encephalopathy. This model may be useful for the preclinical testing of novel and currently available interventions aimed at improving neurologic outcome in infants and children after cardiopulmonary arrest.

Animals↗
PubMed2004

Effects of post-injury hypothermia and nerve growth factor infusion on antioxidant enzyme activity in the rat: implications for clinical therapies.

The pathological sequelae of traumatic brain injury (TBI) include increased oxidative stress due to the production of reactive oxygen species (ROS). Regulation of ROS levels following TBI is determined primarily by antioxidant enzyme activity that in turn can be influenced by nerve growth factor (NGF). Hypothermia is one of the current therapies designed to combat the deleterious effects of TBI. However, it has been shown to suppress post-trauma increases in NGF levels in rat brain. The present study sought to determine whether post-injury hypothermia also impairs the antioxidant response to injury, and if such an effect could be reversed by infusion of exogenous NGF. We employed a lateral controlled cortical impact injury model in rat, followed by moderate hypothermia treatment with supplemental intracerebroventricular infusion of NGF or vehicle. The time course of changes in post-injury/intervention levels of NGF and activity of three major enzymes responsible for ROS scavenging, catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), was determined in the hippocampus. Relative to levels in injured, normothermic animals, hypothermia treatment not only suppressed NGF levels, but also attenuated CAT and GPx activity, and increased SOD activity. Infusion of NGF in injured, hypothermia-treated animals was ineffective in restoring hippocampal antioxidant enzymes activity to levels produced after injury under normothermic conditions, although it was able to increase septal cholinergic (choline acetyltransferase) enzyme activity. These results have implications for clinical treatment of TBI, demonstrating that moderate hypothermia suppresses NGF and the antioxidant response after TBI; the latter cannot be countered by exogenous NGF administration.

Animals↗