Experimental Head Trauma Research Articles

Investigation of Myelin Basic Protein Activity in Determining Neuronal Damage in Rats with Experimental Head Trauma

Amaç: Çalışmamızda deneysel olarak oluşturulan kafa travması sonrası sıçanlarda hafif travmatik beyin hasarı meydana getirilmiştir. Amacımız alınan serum örneklerinde myelin basic protein (MBP) düzeyinin akut dönemde travmatik beyin hasarını göstermede tanısal değerini araştırmaktır.
 
 Gereç ve Yöntemler: Çalışmamızda toplam 40 adet erişkin Spraque-Dawley cinsi sıçan kullanılmıştır. Denekler kontrol grubu (n=8) ve 4 ayrı deney grubu (n=8) olarak 5 gruba ayrıldılar. Travma mekanizması oluşturulurken Marmarou ve ark.’nın tanımladığı model modifiye edilerek uygulandı. Yaptığımız modelde ağırlıkları ve yükseklikleri farklı olan bilyeler serbest düşme yöntemiyle bırakıldı. Sırasıyla 0.05, 0.1, 0.2, 0,4 newton şiddetinde travma oluşturulması hedeflendi ve sırasıyla A, B, C, D grubu olarak adlandırıldı. Travma gerçekleştirildikten 2 saat sonra sıçanlardan alınan kanlarda MBP düzeyi araştırıldı.
 
 Bulgular: Kontrol grubu ile karşılaştırıldığında kan MBP seviyeleri A ve B grubunda anlamlı yüksek saptandı. Gruplar kendi arasında karşılaştırıldığında ise B ve C grup arasında anlamlı farklılık vardır. Aynı şekilde A ve C ile A ve D grubu arasında da anlamlı fark saptanmıştır. Dört grup kendi arasında karşılaştırıldığında travma şiddetiyle MBP’nin kandaki düzeyi arasında korelasyon görülmemiştir.
 
 Sonuç: Travma şiddetinin farklı olduğu gruplarda değerlerin farklı olması MBP artışının sekonder sebeplere de bağlı olma ihtimalini güçlendirmektedir. MBP kafa travmasında TBH’yı değerlendirmek açısından değerli bir biyobelirteç olabilir ancak günümüzde MBP için yapılan çalışmalar yeterli değildir.

Histopathological efficacy of tacrolimus in an experimental head trauma study.

This study aimed to investigate the protective effect of tacrolimus (FK506), an immunosuppressive agent, on secondary brain damage in rats with experimental head trauma. 40 Sprague-Dawley rats, aged 10-12 weeks and weighing 250-350 g, were used without gender selection. The subjects that were divided into five groups of 8 rats per group (sham control, negative control, positive control, vehicle control, and treatment) were sacrificed 1 month after head trauma was induced under appropriate conditions, their brains were then removed en bloc and evaluated histopathologically. Secondary brain injury was evaluated with the immunoreactive score (IRS) after Glial Fibrillary Acid Protein staining of gliosis that would occur in brain tissue. The evaluation of the histopathological IRS values of all groups showed significant statistical differences between all groups. The pairwise group comparison revealed the highest increase in IRS value in the treatment group (p<0.05), with no statistical significance despite the increase in the negative control, positive control, and vehicle control groups. The sham group had the lowest rate of severe histopathological reaction score. It was observed that the group treated with FK506 had a statistically significant increase in gliosis in the traumatic area compared to the other control groups. This shows that FK506 cannot prevent and even increase gliosis by a mechanism that has not yet been clarified. In conclusion, it is obvious that the FK506 immunosuppressive agent does not reduce post-traumatic brain injury; on the contrary, it increases gliosis.

Murine adolescent versus adult brain injury outcomes are improved after brief oxygen exposure

<h3>Research Objectives</h3> Traumatic optic neuropathy (TON) is a significant cause of visual impairment after head trauma and has few effective treatment options. In a mouse model of TON we previously noted post-injury apnea led to immediate mortality in adolescents and brief exposure to 100% oxygen reduced the mortality rate. We hypothesized that oxygen exposure may have an effect on the pathophysiology and functional deficits associated with TON and age at injury might modulate these effects. <h3>Design</h3> This was a randomized controlled preclinical intervention study of brief oxygen supplementation after experimental head trauma. Mice were followed for 7 days after injury. <h3>Setting</h3> Preclinical research laboratory. <h3>Participants</h3> Adult (8 week) and adolescent (6 week) male C57BL/6 mice. <h3>Interventions</h3> Brief oxygen exposure consisted of delivery of 100% Oxygen via hood for a total of five minutes immediately after injury; controls received room air and/or anesthesia only. <h3>Main Outcome Measures</h3> Optokinetic Response was assessed over three days. Retinal tissue was analyzed for protein/RNA expression, and serum assayed for cytokine levels. <h3>Results</h3> Although visual impairment after injury was similar between ages, oxygen more reliably improved OKR deficits in adolescents. Oxygen does not prevent retinal cell loss but does reduce pro-apoptotic markers in the retina in both groups. We anticipate a greater increase in injury-associated markers in adolescent mice compared to adults. <h3>Conclusions</h3> Even though pro-apoptotic markers in retinal cells were reduced, visual deficits persisted. Moreover, brief oxygen exposure appeared to be more beneficial for adolescent mice than for adults. Although preliminary, these results may suggest adolescent mice are more amenable to treatment for TON than adults. <h3>Author(s) Disclosures</h3> There are no conflicts to submission from any author.

INVESTIGATION OF NEUROPROTECTIVE EFFECT OF SHILAGITE EXTRACT IN EXPERIMENTAL HEAD TRAUMA MODEL CREATED IN RATS.

In this study, it was aimed to investigate the neuroprotective effect of shilajit extract in experimental head trauma. Three groups of 33 Sprague Dawley Albino strain male rats were included in the study. Group 1 (n: 11): trauma but not treated. Group 2 (n: 11): trauma and treated with 0.5 mL / rat saline Group 3 (n: 11): 150 mg / kg shilajit extract was administered intraperitoneally in the treatment of trauma. Following the head trauma, the indicated treatments were applied to the 2nd and 3rd groups at the first, twenty-four and forty-eighth hours. Brain tissues and blood samples were taken after the control animals were sacrificed at the 72nd hour in all groups after trauma. Sections prepared from cerebral cortex and ca1 region were examined with hemotoxylin eosin and luxol fast blue staining. Total antioxidant capacity, total oxidant capacity and oxidative stress index were measured from blood samples taken after routine procedures. The number of red neurons and the severity of edema were significantly higher in both the cerebral cortex and the ca1 region in the group treated with trauma only and in the group administered saline after trauma compared to the group that received shilajit extract after trauma. The total antioxidant capacity increased significantly in blood samples taken only from the group treated with trauma and saline in post-trauma treatment compared to the group given post-traumatic shilajit extract, while shilajit extract given due to traumatic brain injury significantly decreased the total oxidant capacity and oxidative stress index values compared to the other groups. . As a result; Shilajit extract has been shown to have a neuroprotective effect in the treatment of acute traumatic brain injury. Our study showed that shilajit may be a useful option in the treatment of secondary brain injury, in humans.

Investigating the Activity of Alpha-synuclein Protein in Determining Neuronal Damage in Rats with Experimental Head Trauma

Çalışmamızın amacı deneysel olarak hafif travmatik beyin hasarı oluşturulan kafa travması modelinde sıçanlardan alınan serum örneklerinde alfa-sinüklein (α-syn) düzeyinin akut dönemde travmatik beyin hasarını göstermede tanısal değerini araştırmaktır. Çalışmamızda toplam 40 adet erişkin Spraque-Dawley cinsi sıçan kullanılmıştır. Denekler kontrol grubu (n=8) ve 4 ayrı deney grubu (n=8) olarak 5 gruba ayrıldılar. Çalışmamızda Marmarou ve ark.’nın tanımladığı model modifiye edilerek uygulandı. Bu modelde farklı yüksekliklerden farklı ağırlıklarda bilyeler serbest düşme yöntemiyle bırakılarak sırayla 0,05, 0,1, 0.2 ve 0,4 Newton şiddetinde travma oluşturulması hedeflendi. Travmanın indüksiyonundan 2 saat sonra sıçanların kalbinden alınan kanlarda α-syn düzeyi araştırıldı. Kontrol grubuna göre kan α-syn düzeyleri ölçüldüğünde, 0,05 ve 0,2 Newton şiddetinde travma oluşturduğumuz gruplarda düşüş görülmüştür. Daha şiddetli travma oluşturduğumuz (0,2 Newton) grup, az şiddetli oluşturduğumuz gruba (0,05 Newton) göre anlamlı olarak daha düşük bulunmuştur. Sonuç olarak farklı şiddetlerde kafa travması oluşturduğumuz sıçanlardan ikinci saatte alınan kan örneklerinden α-syn düzeylerinde anlamlı bir yükselme görülmemiştir. Aksine iki travma grubunda kontrol grubu ile kıyaslandığında düşme görülmüştür. Bu sonuçlar kafa travması sonrası ikinci saatte alınan kanlardan bakılan α-syn düzeyinin TBY için erken dönemde tanısal olarak etkin olmadığını düşündürmektedir.

Can fracture healing be accelerated by serum transfer in head trauma cases? An experimental head trauma model in rats.

Objectives In this study, we aimed to investigate whether the positive union effect caused by head trauma could be transferred between individuals. Materials and methods Seventy-two male rats with an average weight of 375 g were used in this study and divided into four groups including 18 in each group. Group 1 consisted of serum donor rats that were exposed to head trauma, while Group 2 consisted of study rats with long bone fractures that were given the serum obtained from the rats in Group 1, Group 3 included control rats with isolated long bone fractures, and Group 4 included control rats with both head trauma and long bone fractures. For radiological evaluation, the ratio of the width of the callus to the width of the neighboring diaphysis was considered as the callus-to- diaphyseal ratio in the study and control groups. Histopathological and radiological evaluations was made on Days 10, 20, and 30. Results In evaluation of the radiological data regarding the callus- to-diaphyseal ratio, Group 3 was found to have significantly lower radiological values than Group 4 on Day 10 (p=0.006). Group 2 had significantly higher values than Group 3 (p=0.02). On Day 20, Group 2 exhibited significantly higher radiological values than Group 3 (p=0.004), but lower than Group 4 (p=0.032). As for Day 30, Group 2 exhibited significantly higher radiological values than Group 3, but lower than Group 4 (p=0.001). In the evaluation of the Huo scores obtained for histopathological evaluation, there was no significant difference among the groups on Days 10, 20, and 30 (p=0.295, p=0.569, and p=0.729, respectively). Conclusion Our study results suggest that the osteoinductive effect after head trauma can be transmitted between individuals by means of serum transfer.

Effects of Nimodipine and Nigella sativa on Oxidative Stress and Apoptosis in Serum and Brain Tissue of Rats with Experimental Head Trauma.

To investigate whether Nimodipine (N) and Nigella sativa (NS) oil have protective, antioxidant effects in brain injury caused by experimental head trauma. Fifty albino Wistar rats were randomly divided into 5 groups that underwent experimental head trauma. Oxidative parameters were compared in the serum and brain tissue of the different groups. In addition, apoptosis and caspase-3 immunoreactivity were evaluated by histopathological examination. Serum total antioxidant status (TAS) levels were significantly increased in N and N+NS groups when compared with controls (p=0.001, p < 0.01). Tissue TAS levels were significantly higher in the NS and N+NS groups compared to controls (p=0.001, p < 0.01). Total oxidant status levels in the brain tissue were significantly higher in the NS group than in the control group (p=0.021). N and NS were shown to significantly reduce the occurrence of oxidative stress in secondary brain injury due to head trauma. We also found that apoptosis levels decreased in response to N, NS and N+NS treatments after head trauma.

High levels of serum mannose-binding lectins are associated with the severity and clinical outcomes of severe traumatic brain injury

BackgroundMannose-binding lectin (MBL) is a key component of innate immunity. The expression of cortical MBL is up-regulated after clinical and experimental head trauma. This study aimed to assess the association of serum MBL levels with injury severity and long-term clinical outcomes after severe traumatic brain injury (STBI). MethodsSerum MBL levels were measured in 122 patients and 100 healthy controls. Multivariate analyses were used to analyze the relationship between serum MBL levels and trauma severity reflected by Glasgow Coma Scale scores as well as between serum MBL levels and 6-month mortality and unfavorable outcome (Glasgow Outcome Scale score: 1–3). A receiver operating characteristic (ROC) curve was structured to evaluate the prognostic predictive performance of serum MBL levels. ResultsCompared with healthy controls, serum MBL levels of patients were markedly elevated. Using multivariate analyses, serum MBL levels were found to be associated closely with Glasgow Coma Scale (GCS) scores and MBL emerged as an independent predictor for 6-month mortality and unfavorable outcome. Under ROC curve, serum MBL levels and GCS scores possessed similar prognostic predictive values. ConclusionIncreased serum level of MBL was independently associated with head trauma severity and long-term clinical outcomes of STBI.

The effects of erythropoietin, dextran and saline on brain edema and lipid peroxidation in experimental head trauma.

The aim of this study was to investigate the protective effects of erythropoietin, dextran/saline and erythropoietin in combination with dextran/saline on brain edema and lipid peroxidation following traumatic brain injury in rats. In the study, 40 male 3-month-old albino Wistar rats, weighing 250-340 g, were divided into four groups, each consisting of ten rats. Traumatic brain injury was induced in all rats by the weight-drop method, and erythropoietin (5,000 U/kg) and/or dextran and saline (8 ml/kg) solutions were injected intraperitoneally ten minutes after trauma. Control animals received an equal volume of serum physiologic. All rats were sacrificed 24 hours later. Glutathione peroxidase activity and malondialdehyde levels were measured in the left hemisphere, and edema was quantitated by the wet-dry method. Brain edema and the levels of malondialdehyde, the last product of lipid peroxidation in tissues, were decreased variably, and the activity of glutathione peroxidase, an antioxidant enzyme, was increased in others compared with the control group. In this study, it was concluded that the brain edema that developed in rats on which head trauma was induced and the secondary brain damage caused by oxidative stress could be deceased using a combination of erythropoietin, dextran, and saline.

Effect of pregabalin in preventing secondary damage in traumatic brain injury: an experimental study.

BackgroundIn this study we aimed to explore the effects of pregabalin on a traumatic brain injury model in rats.Material/MethodsThis study included 40 adult male Sprague-Dawley rats randomized into 4 groups, each of which contained equal numbers of animals. The control group had no head trauma and thus was not treated. The trauma group had head trauma but was not treated. The pregabalin group had no head trauma but was treated by pregabalin. The trauma + pregabalin group had head trauma treated with pregabalin. The biopsy samples taken from the study animals were histopathologically examined for the presence of edema, inflammation, and neuronal damage.ResultsAll animals in the trauma group had edema, inflammation, and neuronal damage. Four subjects in the control group, 6 in the pregabalin group, and 4 in the trauma + pregabalin group had edema; inflammation was present in 1 subject in the control group, 3 subjects in the pregabalin group, and 3 subjects in the trauma + pregabalin group; neuronal damage existed in 1 subject in the control group, 1 subject in the pregabalin group, and 6 subjects in the trauma + pregabalin group. The trauma group had significantly higher edema and neuronal damage scores than the other groups. Similarly, inflammation was significantly more prevalent in the trauma group than the control and trauma + pregabalin groups.ConclusionsThe results of the present study indicated anti-edema, anti-inflammatory, and neuroprotective effects of pregabalin in an experimental head trauma model in rats. Pregabalin may thus be beneficial in humans with acute TBI by relieving concomitant edema and inflammation.

Effectiveness of GFAP in Determining Neuronal Damage in Rats with Induced Head Trauma.

To determine whether the serum level of glial fibrillary acidic protein (GFAP), an important indicator of neuron damage, correlates with the extent of tissue damage in the rat with induced head trauma and to obtain data in order to avoid unnecessary cranial computed tomography analyses. Three-month-old male Sprague-Dawley rats were used. Rats were divided into 5 groups. The experimental head trauma model was examined in five groups (n=8) as follows: The control group had no intervention; Group 1: Head trauma was induced by dropping a 25 mg ball from a height of 20 cm; Group 2: Head trauma was induced by dropping a 50 mg ball from a height of 20 cm; Group 3: Head trauma was induced by dropping a 50 mg ball from a height of 80 cm; Group 4: Head trauma was induced by dropping a 100 mg ball from a height of 80 cm. Thus, according to the Newton's Law, respectively 0.05, 0.1, 0.2 and 0.4 N trauma was created. Serum GFAP levels were analyzed and the damage to cerebral tissues was evaluated in all groups. We determined that number of apoptotic cells and particularly the number of GFAP (+) protoplasmic astrocytes at the perilesional region of the cortex increased in association with the increased serum GFAP level as long as the severity of the trauma increased. Serum GFAP concentration can be used as a marker of the severity of head trauma and traumatic brain injury. However, more animal studies are required to reflect this result in clinical practice.

Possible nitric oxide modulation in the protective effects of rutin against experimental head trauma–induced cognitive deficits: behavioral, biochemical, and molecular correlates

BackgroundTraumatic head injury is turning out to be a major cause of disability and death. Nitric oxide (NO), an intercellular messenger plays a crucial role in the pathophysiology of several neurologic disorders. Therefore, the present study was designed to investigate the effects of rutin, a well-known flavonoid against cognitive deficits and neuroinflammation associated with traumatic head injury and the probable role of NO pathway in this effect. Materials and methodsWistar rats were exposed to head trauma using weight drop method and kept for a postsurgical rehabilitation period of 2 wk. Later, animals were administered with rutin (20, 40, and 80 mg/kg; per oral) alone and in combination with NO modulators such as NG-nitro-L-arginine methyl ester and L-arginine, daily for another 2 wk. ResultsHead injury caused impaired spatial navigation in Morris water maze test and poor retention in elevated plus maze task. Furthermore, there was a significant rise in acetylcholinesterase activity, oxidative stress, neuroinflammation (tumor necrosis factor α), and neuronal apoptosis (caspase-3) in both cortex and hippocampal regions of traumatized rat brain. Rutin significantly attenuated these behavioral, biochemical, and molecular alterations associated with head trauma. Furthermore, pretreatment of NG-nitro-L-arginine methyl ester (10 mg/kg, intraperitoneally), a nonspecific nitric oxide synthase inhibitor, with subeffective dose of rutin (40 mg/kg) potentiated the protective effects; however, pretreatment of L-arginine (100 mg/kg; intraperitoneally), an NO donor, reversed the effects of rutin. ConclusionsThe present study suggests that NO modulation could possibly be involved in the neuroprotective effects of rutin against head trauma–induced cognitive deficits, neuroinflammation, and apoptotic signaling cascade.

Effect of erythropoietin on brain tissue after experimental head trauma in rats

Background The purpose of this study was to investigate the effect of EPO on LPO, on ultrastructural findings, and on antiapoptotic bcl-2 and survivin gene expressions after TBI. The authors also compared the activity of EPO with that of MPSS. Methods Wistar rats were divided into 6 groups: sham-operated, control, moderate TBI-alone (300 g/cm), TBI + EPO-treated (1000 IU/kg), TBI + MPSS-treated (30 mg/kg), and TBI + vehicle-treated (0.4 mL albumin solution) groups. Results Compared with the levels in control and sham-operated animals, LPO was significantly elevated in rats in the trauma-alone group. The administration of EPO and MPSS significantly decreased the LPO levels ( P < .05). Trauma also increases the antiapoptotic bcl-2 gene expression significantly at 24 hours postinjury ( P < .05), but it has no effect on survivin expression. The EPO and MPSS treatments caused significant elevation in both gene expressions ( P < .05). It is also showed that MPSS has more protective effect than EPO on brain ultrastructure, especially on the structure of small- ( P < .05) and medium-sized myelinated axons, after TBI. Conclusions EPO has protective effects after moderate TBI, and this effect seems better than MPSS on antiapoptotic gene expression and LPO. The protection of cerebral subcellular organelles after traumatic injury is more prominent in MPSS-treated animals than EPO-treated animals quantitatively. This experimental study indicates that the benefits of EPO in the management of TBI have promising results and prompts further studies on the difference between EPO and MPSS in histopathological findings at the subcellular level.

Plasma vitamin E and selenium levels in rats with head trauma

Background Free radicals play an important role in brain damage induced by a head trauma. In this study, we examined the prevention of brain damage that occurs after oxidative stress in rats that had undergone an experimental head trauma and the determination of plasma levels of vitamin E and selenium, which are recognized as antioxidant agents. Methods In this study, adult male Sprague-Dawley rats were used. Rats were divided into 2 groups. In the first group (control group, n = 10), pretraumatic plasma selenium and vitamin E levels were investigated and rats were not traumatized. In the second group (trauma group, n = 10), posttraumatic plasma selenium and vitamin E levels were investigated at the 6th and 24th hours in traumatized rats. Results In the control group, the plasma selenium level was 107 ± 8.113 μg/L, whereas vitamin E level was 1.310 ± 0.048 mg/dL. In the trauma group, the plasma selenium level was 79.93 ± 3.130 μg/L at the 6th hour and 74.74 ± 2.947 μg/L at the 24th hour, whereas the vitamin E level was 1.211 ± 0.056 mg/dL at the 6th hour and 1.136 ± 0.044 mg/dL at the 24th hour. Normal plasma selenium and vitamin E levels were significantly reduced in the early period after trauma. Conclusion Because of oxidative stress that occurs directly after a head trauma, vitamin E and selenium depletion occurs in the early period. This condition supports the idea that brain damage can be reduced if decreased antioxidants are replaced when a head trauma occurs. We believe that these findings will guide and assist in future studies to develop clinical management strategies to prevent brain damage induced by head trauma.

Modified Experimental Mild Traumatic Brain Injury Model

Experimental models of traumatic brain injury (TBI), using a variety of techniques and species, have been devised with the aim of producing repeatable lesions resembling those found in head injuries. There are various TBI models mentioned in the literature. In experimental head trauma models, emphasis has been placed on the severe head injuries. There are only a few models developed to study mild traumatic brain injury (MTBI). In fact, MTBI is as important a problem as severe head injuries for neurosurgeons. Fifty-six male Sprague-Dawley rats were subjected to MTBI with a weight-drop device, which was described by Marmarou et al. The said model was used in its original form as well as in modified forms by employing different weights dropped from the same height. Animals were divided into four groups of 14 rats as follows: Group I (n=14), head injury was induced using 450 g-1 m weight-height impact; Group II (n=14), head injury was induced using 350 g-l m weight-height impact; Group III (n=14), head injury was induced using 300 g-1 m weight-height impact; Group IV (n=14), control group, no injury was applied. Animals were evaluated neurologically, physiologically, electrophysiologically, and histopathologically. Group I and II animals (450 and 350 g-1m weight-height impact, respectively) showed the symptoms of severe head injury, whereas Group III animals (300 g-l m) showed more MTBI symptoms. We recommend the application of the modified MTBI model used for group III (300 g-l m weight-height impact) as the most appropriate and the simplest model for future MTBI studies.

Effect of gamma‐hydroxybutyric acid on tissue Na+,K+‐ATPase levels after experimental head trauma

A failure of the Na(+),K(+)-ATPase activity (which is essential for ion flux across the cell membranes) occurs in many pathological conditions and may lead to cell dysfunction or even cell death. By altering the concentration of specific opioid peptides, gamma-hydroxybutyric acid (GHB) may change ion flux across cell membranes and produce the 'channel arrest' which we assumed will inhibit the failure of Na+,K(+)-ATPase activity and therefore lead to energy conservation and cell protection. Therefore we planned this study to see the effects of GHB at two different doses on Na(+),K(+)-ATPase activity in an experimental head trauma model. Forty New Zealand rabbits were divided equally into four groups: group I was the sham-operated group, group II (untreated group), group III received head trauma and intravenous (i.v.) 500 mg/kg GHB and group IV received head trauma and i.v. 50 mg/kg GHB. Head trauma was delivered by performing a craniectomy over the right hemisphere and dropping a weight of 10 g from a height of 80 cm. The non-traumatized (left) side was named as 'a' and the traumatized (right) side as 'b'. One hour after the trauma in groups II and III and craniotomy in group I, brain cortices were resected from both sides and in group I only from the right side was the tissue Na-K-ATPase activity determined. The mean +/- SD of Na(+),K(+)-ATPase levels of each group are as follows: group I - 5.97 +/- 0.55; group IIa - 3.90 +/- 1.08; group IIb - 3.58 +/- 0.90; group IIIa - 5.53 +/- 0.60; group IIIb - 5.33 +/- 0.88; group IVa - 5.05 +/- 0.72; group IVb - 4.93 +/- 0.67. The Na(+),K(+)-ATPase levels of group IIa, IIb, IVa and IVb were significantly different from group S (P < 0.05). There were also significant differences between group IIa and groups IIIa and IVa; group IIb and groups IIIb and IVb (P < 0.05). We conclude that GHB is effective in suppressing the decrease in Na(+),K(+)-ATPase levels in brain tissue at two different dose schedules after head trauma.

Effect of gamma-hydroxybutyric acid on lipid peroxidation and tissue lactate level in experimental head trauma.

This study was designed to determine the effects of gamma-hydroxybutyric acid (GHB) on tissue lactate and malondialdehyde (MDA) levels in rabbit brain after experimental head trauma. Thirty New Zealand rabbits were divided equally into three groups: group S was the sham-operated group, group C, and group GHB received head trauma, where group C was the untreated and group GHB was the treated group. Head trauma was delivered by performing a craniectomy over the right hemisphere and dropping a weight of 10 g from a height of 80 cm. GHB was administered 400 mg/kg intravenously for 10 minutes after the head trauma to group GHB. The nontraumatized side was named "1" and the traumatized side was named "2." One hour after trauma, brain cortices were resected from both sides and the concentrations of lactate and MDA were determined. There were significant differences between lactate and MDA levels of group S and all other groups (C1, C2, GHB1, and GHB2) except between lactate levels of group S and group GHB1, the nontraumatized and traumatized sides of groups C and group GHB, group C2 versus group GHB2, and group C1 versus group GHB1 (p < 0.05). Rectal temperature after the administration of GHB in group GHB was found lower than in groups S and C (p < 0.05). These results demonstrate that head trauma leads to an increase in brain tissue lactate and MDA levels, and GHB effectively suppresses the increase of lactate and MDA.

Ultrasound agents may open the blood-brain barrier in rats and aggravate pathologic consequences of experimental head trauma.

Unilateral intracarotid injection of contrast agents may considerably destabilize the blood-brain barrier in rats. This leads to vasogenic edema in the ipsilateral hemisphere. Mortality and extravasation increased significantly when administration of these ultrasound contrast agents was followed by mild traumatic brain injury. Direct administration to the cerebral circulation is, therefore, indicative for edema-related pathology and may amplify the consequences of experimental neurotrauma.

Post-Traumatic Hyperexcitability Is Not Caused by Impaired Buffering of Extracellular Potassium

Impaired extracellular potassium buffering has been proposed as one of the major mechanisms underlying the increased risk for temporal lobe epilepsy after brain injury (D'Ambrosio et al., 1999). The present study systematically tested this hypothesis by measuring the resting [K+]o and recovery of the stimulation-evoked [K+]o increases in the dentate gyrus after experimental head trauma, using a combination of whole-cell recordings and ion-selective microelectrode recordings in rat hippocampal slices. Despite the presence of hyperexcitability, the resting [K+]o was not increased after injury. The faster rate of increase and larger amplitude of the orthodromically evoked [K+]o elevation after head trauma occurred in association with a greater population spike with shorter response latency. Contrary to the assumption in previous studies that the evoked activity in control and injured neuronal circuits is the same during antidromic activation, stimulation of granule cell axons in glutamate receptor antagonists evoked a greater [K+]o increase and a larger population spike. Although perforant path stimulation resulted in a larger [K+]o elevation after injury, the rate of clearance of the [K+]o transients evoked either by neuronal activity or by external application of potassium was not compromised. The [K+]o increase evoked by activation of the presynaptic afferents in isolation was not increased. In addition, the postsynaptic neuronal depolarization and firing evoked by exogenous potassium application was decreased after trauma. These results show that the regulation of [K+]o is not impaired after injury and indicate that the larger [K+]o increase evoked by neuronal activity is a consequence, rather than the primary mechanism underlying post-traumatic hyperexcitability.

Real-time PCR quantitation of FE65 a β-amyloid precursor protein-binding protein after traumatic brain injury in rats

In cases of traumatic brain injury (TBI) in which the patient survived for only a short period of time and was without macroscopic changes at autopsy, it is difficult to diagnose TBI. To detect early diagnostic markers of diffuse axonal injury (DAI), real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in an experimental head trauma model of rat was chosen. The beta-amyloid precursor protein (beta-APP) is a well-known diagnostic marker of DAI which can be detected by immunolabeling as early as 1.5 h after injury. beta-APP has a binding protein, FE65, which is expressed in the brain of Alzheimer's disease patients along with beta-APP, but no involvement with brain injury has been reported. Neuron-specific enolase (NSE) is also a useful marker of DAI. We found that FE65 expression increased dramatically as early as 30 min after injury and decreased after peaking 1 h post-injury, although NSE showed no significant changes. These results suggest that real-time PCR of FE65 mRNA is useful for the diagnosis of DAI in forensic cases.