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Objective To study the protective effect of pure carbachol or combined with dietary fiber on intestinal mucosal barrier of rats after diffuse brain injury (DBI).Methods An adult male Wistar rat model of DBI was reproduced by gravitational shock method. The rats injured and survived after resuscitation were divided into three groups: model group (n = 40), carbachol group (n = 40) and carbachol combined with dietary fiber group (combined group,n = 32). In addition, a control group was established by simply an incision performed on the scalp, and the rats could drink freely (n = 5). In the experimental groups, 2 hours after resuscitation the rats began to receive gavage, 6 hours once, the liquid amount 15 mL/kg should be assured in every 6 hours, and if insufficient, normal saline was supplemented. In model group, normal saline 90 mL/kg was given, in carbachol group, carbachol 300μg/kg was administered and in combined group, carbachol 300μg/kg combined with dietary fiber 60 mL/kg was supplied. At 3 (combined group being excluded), 6, 12, 24 and 48 hours after resuscitation, the rats were anesthetized to collect samples and detect the plasma levels of D-lactate and activity of diamine oxidase (DAO) respectively, and the changes of villus height of small intestine were examined by a light microscope.Results The plasma D-lactate levels and the activities of DAO at any time point in the experimental groups were significant higher than those in control group (allP < 0.01). Along with the prolongation of time, the levels of plasma D-lactate and DAO activities in carbachol and carbachol plus diatary fiber groups were gradually lower than those of the model group, and at 48 hours after injury they reached their valley values [D-lactate (ng/L): 6.32±0.79, 7.46±1.67 vs. 17.65±1.53, DAO activity (kU/L): 0.76±0.01, 0.86±0.01 vs. 2.23±0.15]. Under light microscopy, compared with control group, the villus height of small intestinal mucosa at any time point in any experimental group was gradually lowered, and reached the valley values at 12 hours, then gradually increased , and peaked at 48 hours, the villus height in carbachol group and combined group was higher than that in model group (μm: 265.36±10.20, 261.54±10.38 vs. 247.51±9.39, bothP < 0.05).Conclusion When only carbachol is administered into the rat intestine early after diffuse brain injury in rats, beginning from 6 hours after injury, the protective effect of intestinal mucosal barrier is shown, representing decrease of plasma D-lactate level and DAO activity, amelioration of intestinal mucosal damage and protection of intestinal mucosal barrier; under the same above situation, the carbachol combined with dietary fiber was applied, showing the similar above carbachol protective effects.
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(DBI) in rats by observation on the changes of Homer 1a expression and apoptotic nerve cells . Methods Spraque-Dawlley(SD) rats were randomly ( random number ) divided into control group and severe DBI group .DBI rat model was established according to the de-scription of Marmarou′s diffused brain injury .No injury was done on control group .The changes of neuron pathology were observed by light microscopy and electron microscope .The expression of Homer1a was observed by immunohistochemistry and western blot .The quan-tity of apoptotic cells was measured by terminal deoxynucleotidyl transfernase medicated nick end labeling ( TUNEL) method. Results The death rate of rats in severe DBI group was 49.3%.Compared with the control group , the ultrastructures in hippocampal neurons in-cluding organelle , axonal and capillary were damaged seriously after injury , the survival rate of nerve cells decreased significantly at 1 h after injury ([99.4 ±0.6]%vs [94.4 ±5.6]%, P<0.05), and peaked at 72 h ([99.2 ±0.8]%vs [54.7 ±33.8]%, P<0 .05) in DBI group.The expression of Homer1a protein increased significantly at 1 h after injury(0 .136 ±0.024 )and peaked at6 h(0.178 ± 0.028) and maintained to 24 h (0.176 ±0.027), while decreased at 48 h (0.145 ±0.02)and 72 h (0.117 ±0.012) in DBI group;the expression of Homer 1a was obviously higher at each time point in DBI group than that in control group (P <0.05).The apoptoticindex of TUNEL positive cells increased at 6 h and demonstrated significant difference at 72h in comparison to control group ([41.78 ±3 .96]%vs [1.92 ±0.22]%, P<0.05).The correlation analysis indicated that Homer1a expression from 1~24 h and 24 h~72 h was related to the survival rate of nerve cells ( r=-0.726, P<0.05; r=0.842, P<0.05) and the quantity of TUNE positive cells(r=0.738, P<0.0;5 r=-0.898, P<0.05). Conclusion The dynamic expression of Homer1a in hippocampus after severe DBI can reflect nerve cell loss.
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Objective To explore the effects of SB203580(a MAPK inhibitor) on the expression of Homer1a in hippocampus and learning-memory after diffuse brain injury in rats.Method Male Sprague-Dawlley rats were divided randomly into three groups:control group,diffuse brain injury(DBI) group and DBI+ SB203580 group (peritoneal injection,0.01 μg/kg).Morphological changes of neuronal cells were observed by electron microscope and the expression of Homer1a and phosphorylated p38MAPK was detected by immunohistochemistry and learning and memory functions were performed with Morris water maze (MWM).Results Compared with control group,ultrastructure of neuronal cells and synapses were significantly.The levels of phosphorylated p38MAPK(76.98±16.64,2.28±0.40,P＜0.05) and Homer1a (62.96± 12.74,1.28±0.10,P＜0.05)respectively were increased after injury impaired.MWM test showed that the escaping latency was prolonged((74.64± 8.96)s,(24.96±4.98)s,P＜0.05) and the frequency of crossing the platform was decreased(4.48± 1.12,12.65±2.36,P＜0.05).Compared with the model group,SB203580 decreased ultrastructure impariment in neuronal cells and synapses and decreased phosphorylated p38MAPK expression(54.82± 12.48,76.98± 16.64,P＜0.05) and increased Homer1a expression(54.82 ±12.48,76.98± 16.64,P＜0.05).MWM test showed that the escaping latency was shorten ((46.72±6.58) s,(74.64± 8.96) s,P＜0.05),and the frequency of crossing the platform was increased (7.56± 1.20,4.48± 1.12,P＜0.05).Conclusion SB203580 improves the learning-memory recovery after DBI,which is related to inhibition of p38MAPK activation and increasing Homer1a expression.
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Objective To study the changes of hearing function and cochlear morphology on diffuse brain in-jury model in rat .Methods One hundred and fifty SD rats with normal hearing were randomly divided into five groups ,each group consisted of 30 SD rats ,including a control group and four experimental groups which endured diffuse brain injury(DBI) from one to four weeks .Diffuse brain injury model of rats were established ,then ABR , 40 Hz AERP and ASSR examination ,light microscopy ,electron microscopy were used to evaluate the change of hearing function and morphology .Results The difference of ABR ,40 Hz AERP and ASSR thresholds between the experimental and the normal control group were significant (P<0 .05) .The thresholds of ABR ,40HzAERP and AS-SR were increased in the first week of DBI ,then the threshold continuously increased in the second and third week , at last the threshold decreased in the fourth week .The results under scaning electron microscope demonstrated that the ciliums of the majority of outer hair cells lodged in the first week of DBI .The results under transmission electron microscope showed that in the first week of DBI ,there were edema and denuration of mitochondrial ,mitochondrial cristaes were obscured or disappeared .The changes were deteriorate in the second and third week ,whereas the changes were mitigatal in the fourth week .Conclusion Cochlear morphology and hearing damage were observed in diffuse brain injury model of rats .
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BACKGROUND: Edaravone can alleviate brain injury and improve neurological functions and symptoms. This study aimed to investigate the effect of edaravone on the p38Mitogen-activated protein kinases/Caspase-3 (p38MAPK /Caspase-3) pathway after diffuse brain injury (DBI) in rats. METHODS: DBI models were established according to the description of Marmarou's method. A total of 250 rats were divided (random number) into four groups: control group (CG, n=45), model group (MG, n=77), low-dose edaravone group (n=67, dosage 5 mg/kg) and high-dose edaravone group (n=61, dosage 10 mg/kg). After 1, 6, 24, 48, and 72 hours after injury, brain tissues were collected. The changes of neuron morphous in the hippocampal region were observed through Nissl staining. The expression levels of phosphorylated p38MAPK and caspase-3 were detected by immunohistochemistry and Western blotting respectively. Learning and memory function were tested with Morris water maze from the 3rd to 7th day after injury. RESULTS: Some neurons had histopathologic changes of necrosis and apoptosis in the model group compared with the control group. The phosphorylated p38MAPK expressions increased at 1, 6, 4, and 48 hours (P<0.05), but no significant difference was observed at 72 hours (0.54±0.19 vs. 0.40±0.14, P>0.05). Caspase-3 expressions increased at 6, 24, 48, and 72 hours respectively (P<0.05), but there was no significant difference at 1 hour (0.59±0.29 vs. 0.40±0.17, P>0.05). From the 3rd to 6th day during the Morris water maze test, the latency to find the platform was significantly prolonged (P<0.05) and times of rats crossing the platform was decreased on the 7th day (2.28±1.18 vs. 8.20±1.52, P<0.05). The phosphorylated p38MAPK expressions decreased at 6, 24 and 48 hours respectively in the low dose edaravone group compared with the model group (P<0.05), whereas no significant difference was seen at 1 hour (1.66±0.80 vs. 1.85±0.86, P>0.05). Caspase-3 expression decreased at 6, 24, 48, and 72 hours (P<0.05). The latency to find the platform was significantly shortened (P<0.05), and times of rats crossing the platform increased (4.17±1.15 vs. 2.28±1.18, P<0.05). The above mentioned parameters changed more significantly in the high-dose edaravone group than in the low-dose edaravone group. CONCLUSION: Edaravone can alleviate brain tissue damage after DBI, inhibit p38MAP signal activation after early injury, reduce the expression of caspase-3, and promote the recovery of neurological function in the late period.
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Objective To develop-the rat model of diffuse brain injury(DBI)and to observe the pathophysio logical alteration of the rats after.traumatic injury.Methods A modified Marmarou's traumatic device W88 used to establish the animal model of diffuse brain injury with different degree through changing the impact condition that was applied on the rat brain(including 80cm 450g,120 cm 450g and 180cm 400g);the animal model was evaluated by observing the variations of nervous system signs,vital signs,sensorimotor function,and morphological changes of brain tissue in the rats that have received different impacts.Results The significant changes in nervous system signs,vital signs and sensorimotor function had been observed in all rats that were subjected to the different impact.The pathologic changcs of DBI in rats brain could he found in all groups.Moreover,this characteristic changes would have became more significant following the traumatic iaiury when the impact energy was increased.Conclusion The rat model of graded diffuse brain injury have been developed successfully.The moderate impact(120cm 450g)could produce low animal death rate and result in obvious pathologieal alterations in the injured rat brain.This impact condition would be suitable to be used in the study about DBI.
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Objective To investigate the dynamics of the level of S100 in cerebrum, brainstem, and serum following the diffuse brain injury in rats and provide the experimental evidences for estimating injury time. Methods ELISA was used to determine whether S100 protein is changed after diffuse brain injury in rats. Forty rats were sacrificed at 0.5 hour, 2 hours, 4 hours, 12 hours, 24 hours, 3 d and 7 d after diffuse brain injury and normal rats as control. Results The level of S100 in cerebrum, brainstem, and serum increased, followed by a decrease, and then further increased. The level of S100 could be detected to increase at 30 minutes and reached the peak at 4 hours after DBI. The level decreased gradually to the normal at 1d and till 3 d formed the second peak. The level returned to the normal at 7d following injury again. In the postmortem injury groups, there were no significant changes compared to the control group. Conclusion The present study showed that the time-dependent expression of S100 is obvious following diffuse brain injury in rats and suggested that S100 will be a suitable marker for diffuse brain injury age determination.
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Objective: To investigate the dynamics of the level of S100 in cerebrum, brainstem, and serum following the diffuse brain injury in rats and provide the experimental evidences for estimating injury time. Methods: ELISA was used to determine whether S100 protein is changed after diffuse brain injury in rats. Forty rats were sacrificed at 0. 5 hour, 2 hours, 4 hours, 12 hours, 24 hours, 3 d and 7 d after diffuse brain injury and normal rats as control. Results: The level of S100 in cerebrum, brainstem, and serum increased, followed by a decrease, and then further increased. The level of S100 could be detected to increase at 30 minutes and reached the peak at 4 hours after DBI. The level decreased gradually to the normal at 1d and till 3 d formed the second peak. The level returned to the normal at 7d following injury again. In the postmortem injury groups, there were no significant changes compared to the control group. Conclusion: The present study showed that the time-dependent expression of S100 is obvious following diffuse brain injury in rats and suggested that S100 will be a suitable marker for diffuse brain injury age determination.
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Our study was designed to determine whether methylprednisolone exerts a beneficial effect after experimental moderate diffuse brain injury and whether this possible beneficial effect is affected by the dosage, the timing of administration, and the methods of treatment. A total of 200 anesthetized adult rats were injured utilizing a weight-drop device through a Plexiglas guide tube. These rats were divided into eight groups: Group 1 (n=35) was assigned to receive no methylprednisolone after impact (control group), Group 2 (n=25) received an initial intraperitoneal administration of methylprednisolone with a dose of 5 mg/kg at 1hour after cranial impact, followed by administration with a maintenance dose of 5 mg/kg/4 hours. Group 3 (n=25), group 5 (n=25), and group 7 (n=20) received an initial 30 mg/kg at 1 hour, 4 hours, and 8 hours, respectively without a maintenance dose. Group 4 (n=25), group 6 (n=25), and group 8 (n=20) received an initial 30 mg/kg at 1 hour, 4 hours, and 8 hours after impact, with a maintenance dose of 15 mg/kg/4 hours. Measured water content of brain tissue expressed the amount of water as the difference between fresh and dry weight. At 48 hours after impact, the water content in group 4 and 6 were significantly lower than group 1. Mean SD was 61.4 0.37% in group 4 (p0.1), group 3 (p>0.5), group 5 (p>0.6), group 7 (p>0.1), and group 8 (p>0.5). Groups treated with mega dose before 4hours after head injury, including maintenance dose, showed beneficial effects. Our study suggests that the efficacy of methylprednisolone in head injury was related to the dosage, the timing of administration, and method of treatment.
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Rats , Animals , Brain Edema , Brain Injuries/drug therapy , Dose-Response Relationship, Drug , Injections, Intraperitoneal , Methylprednisolone/therapeutic use , Neuroprotective Agents/therapeutic use , Rats, Sprague-DawleyABSTRACT
The present study was undertaken to examine the ability of a single large intraperitoneal dose of methylprednisolone(15, 30, 40, 60mg/kg) to modify the evolution of diffuse brain injury(DBI) in rats undergoing a contusion injury of 400gm-1m. Twenty five Sprague-Dawley rats were divided to five groups. Group 1 was not treated after cranial impact as control. Rats in group 2, 3, 4, 5 were treated with 15-mg/kg, 30-mg/kg, 40-mg/kg, 60-mg/kg methylprednisolone dose at 1 hour after injury, respectively. After 24 hours, these rats were sacrificed, and the water content of the whole brain were measured. When the water content was assumed as the criterion of brain edema, there was significant difference between control group(71.03+/-.42%) and group 2(67.34+/-.07%), group 3(66.43+/-.36%), group 4(64.52+/-.11%)(p0.01). This study shows that megadose of methylprednisolone in 15, 30, or 40mg/kg reduces the brain edema, and the its effect is biphasic in that the 60-mg/kg methylprednisolone dose is ineffective.
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Animals , Rats , Brain , Brain Edema , Brain Injuries , Contusions , Hand , Methylprednisolone , Rats, Sprague-DawleyABSTRACT
A retrospective study of predictors determing outcome was carried out in a consecutive series of 104 patients, who had suffered from diffuse brain injury between December 1989 and April 1995, at the Department of Neurosurgery, Soonchunhyang University Hospital. The clinical, laboratory and radiological factors affecting the outcome in patients were analyzed and correlation between the factors and Glasgow outcome scale were statistically assessed. The major results were as follows: Significant predictors of poor outcome were old age, time interval within 5 hours from onset to admission, full dilated pupils or anisocoria, lower Glasgow coma scale, seizure, body temperature above 38 degrees C, PaO2 below 70mmHg, blood sugar above 160mg/dl, platelet count less than 100,000/mm3, prothrombin time less than 80%, lesions in more than 2 locations on CT & MRI and operative cases. Glasgow coma scale, age and temperature were demonstrated as the most significant predictors among the above factors by discriminant analysis. 2) Sex , kind of accidents, associated injuries, systolic blood pressure, pulse rate, respiration rate, PaCO2, base excess, serum sodium, bleeding time, coagulation time, and skull fracure were not significant influences on the outcome. According to the above results, the predictors of poor outcome should be considered as factors in assessing prognosis for treatment of diffuse brain injury.
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Humans , Anisocoria , Bleeding Time , Blood Glucose , Blood Pressure , Body Temperature , Brain Injuries , Glasgow Coma Scale , Glasgow Outcome Scale , Heart Rate , Magnetic Resonance Imaging , Neurosurgery , Platelet Count , Prognosis , Prothrombin Time , Pupil , Respiratory Rate , Retrospective Studies , Seizures , Skull , SodiumABSTRACT
In the last decade Computed Tomography(CT) has played a critical role in the diagnostic evaluation of the patients with focal brain injury. But it is apparent from pathologic studies that CT underestimates the severity of the many forms of cerebral injury such as primary brain stem injury, non-hemorrhagic cortical contusion and diffuse axonal injury(DAI). Magnetic Resonance Imaging(MRI), however, has been shown to be highly sensitive in detecting diffuse brain injury(DBI). Among the consecutive 13 cases of DBI patients in this series for 10 months, twelve patients were verified as MR evidence of injury in prospective studies. The anatomical distribution of the injuries were 11 cases of corpus callosal lesion, 6 cases of lobar white matter lesion, 1 case of primary brain stem lesion. The sensitivities of MR imaging in detecting the primary lesion were 76.9%(10/13) in T1WI and 92.3%(12/13) in T2WI. In DBI, patients with callosal injuries had higher incidence(8/12) than lobar white matter and primary brain stem lesion, the corpus callosal atrophy by midsaggital MR imaging and behavioral seguellae in survivous of severe head injury implicate the corpus callosal injury and degeneration. More accurate detection and delineation of traumatic lesions with MR should permit more accurate prediction of neurologic and cognitive recovery and assist in optimizing form of treatment.
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Humans , Atrophy , Axons , Brain , Brain Injuries , Brain Stem , Craniocerebral Trauma , Magnetic Resonance Imaging , Prospective StudiesABSTRACT
The present study compares the outcome of adult and pediatric patients with severe diffuse brain injury, and analyzes factors affecting the prognosis related to age difference. Of 912 patients admitted with head injury during the past three years, 223(1.7%) patients were identified as severe diffuse brain injury. Among the 223 patients. 100 patients were 15 years of age or less as the pediatric group. The mortality rate for pediatric and adult group was 39.0% and 48.8%, respectively. The common factors affecting poor prognosis for both groups were Glasgow Coma Scale(GCS) of 5 or less, papillary abnormality, hypoxia(PaO2<60 mmHg), the presence of skull fracture(basilar skull fracture in children, and basilar or vault skull fracture in adult group), diffuse brain swelling, subarachnoid hemorrhage, intraventricular hemorrhage, and thin subdural hematoma. The factors affecting prognostic difference between the adult and pediatric group with diffuse brain injury were the presence of vault skull fracture(p<0.01) and diffuse brain swelling(p<0.05). In patients associated with vault skull fracture or diffuse brain swelling, adult group had a significantly poorer outcome than child group.
Subject(s)
Adult , Child , Humans , Brain , Brain Edema , Brain Injuries , Coma , Craniocerebral Trauma , Hematoma, Subdural , Hemorrhage , Mortality , Prognosis , Skull , Skull Fractures , Subarachnoid HemorrhageABSTRACT
From January 1987 to December 1989, we tried to treat conservatively for 44 patients with acute (within 24 hours) subdural hematoma at the Soonchunhyang University Chonan Hospital. The conservative treatment was performed for the patients who furfilled the following criteria ; 1) the thickness of the hematoma was smaller than the skull bone thickness(about 1cm), 2) the pupils were normal or rapidly became normal, and 3) there was little midline shift or little mass effect by the hematoma itself. The mean age was 36.8 years and the male to female ratio was 31 : 11. The mean interval from injury to CT scanning was 2.1 hours. All Patients were arrived within 5 hours after head injury. The mean GCS value on admission was 11.5. Abnormal pupils were found in 13 patients(29.5%). Most common cause of injury was road traffic accident. The mean thickness of the hematoma was 5.9mm and the mean volume of the hematoma was 12.6ml. The mean degree of midline shift was 2.5mm. Compression of the basal cistern, mesencephalic cistern and the lateral ventricle was observed in 20(45.5%), 17(38.6%), and 23 patients(52.3%), respectively. Skull vault fracture was present in 25 patients(56.8%). In the majority of the patients, they became alert within three days. Twenty-four patients(54.5%) were recovered without any deficits or sequelae. Only one patient(2.3%) required operative removal on the 9th hospital day(HD) due to enlarged hematoma and delayed recovery. Another patient required shunt operation due to communicating hyprocephalus 22 months later. Overall mortality rate was 25.0%. We discussed on the possible harmful effect of surgery and rationale of the conservative treatment for the thin ASDH.
Subject(s)
Female , Humans , Male , Accidents, Traffic , Brain Injuries , Craniocerebral Trauma , Hematoma , Hematoma, Subdural , Hematoma, Subdural, Acute , Lateral Ventricles , Mortality , Pupil , Skull , Tomography, X-Ray ComputedABSTRACT
A retrospective study on 107 cases of acute(within 24 hours) subdural hematoma(ASDH) with special reference to the size is presented. The thin ASDH is defined as the hematoma of which thickness is less than 3 mm in the printed CT film(true thickness about 10 mm). 45 cases are the thin ASDH and 62 cases are the not-thin ASDH. Age, Glasgow coma score, pupil, CT finding, operation finding, operation method, interval from injury to CT and operation, and outcome at 1 month are compared and analysed with chi square tests. The most significant difference is the high surgical mortality (92.6%) in the thin ASDH despite of the fact that there are no significant bad prognostic factors. This difference might be due to the fact that diffuse brain injury is more commonly associated with the thin ASDH and suggested that the thin ASDH should be managed differently from the not-thin ASDH.