OBJECTIVE: With the technical support from department of mechanical engineering, Korea Advanced Institute of Science and Technology(KAIST), we began to develop a better head trauma model named "Chung-Ang University Hospital Model 1.0(CAUH-1)" in March 2001 and completed it August 2001. In addition, we conduct functional tests(postural reflex, balance beam test, rotarod test, and etc) to verify this model. METHODS: Twelve four hours after moderate head injury(air tank pressure : 125psi, impact velocity: 1.34m/sec, depth of deformation : 2.5mm, dwell time : 84.5msec), we conducted various functional tests. Then, we compared the results with those of sham group. RESULTS: Using this device, we revive neurobehavioral changes(decreased reflexes, hemiparesis, decreased vestibulo-motor function) occuring after human head trauma. CONCLUSION: In our opinion, this is a very useful experimental head trauma model and will be helpful to many head trauma researchers.
Craniocerebral Trauma ; Head ; Humans ; Korea ; Paresis ; Reflex ; Rotarod Performance Test

OBJECTIVE: To evaluate the effects of epidural electrical stimulation (EES) and repetitive transcranial magnetic stimulation (rTMS) on motor recovery and brain activity in a rat model of diffuse traumatic brain injury (TBI) compared to the control group. METHODS: Thirty rats weighing 270-285 g with diffuse TBI with 45 kg/cm2 using a weight-drop model were assigned to one of three groups: the EES group (ES) (anodal electrical stimulation at 50 Hz), the rTMS group (MS) (magnetic stimulation at 10 Hz, 3-second stimulation with 6-second intervals, 4,000 total stimulations per day), and the sham-treated control group (sham) (no stimulation). They were pre-trained to perform a single-pellet reaching task (SPRT) and a rotarod test (RRT) for 14 days. Diffuse TBI was then induced and an electrode was implanted over the dominant motor cortex. The changes in SPRT success rate, RRT performance time rate and the expression of c-Fos after two weeks of EES or rTMS were tracked. RESULTS: SPRT improved significantly from day 8 to day 12 in the ES group and from day 4 to day 14 in the MS group (p<0.05) compared to the sham group. RRT improved significantly from day 6 to day 11 in ES and from day 4 to day 9 in MS compared to the sham group. The ES and MS groups showed increased expression of c-Fos in the cerebral cortex compared to the sham group. CONCLUSION: ES or MS in a rat model of diffuse TBI can be used to enhance motor recovery and brain activity.
Animals ; Brain ; Brain Injuries* ; Cerebral Cortex ; Electric Stimulation* ; Electrodes ; Models, Animal ; Motor Cortex ; Rats* ; Rotarod Performance Test ; Transcranial Magnetic Stimulation*

OBJECTIVE: A study of the histopathologic and neurobehavioral correlates of cortical impact injury produced by increasing impact velocity using the controlled cortical impact(CCI) injury model is studied. METHODS: Twenty-four Sprague-Dawley rats (200~250g) were given CCI injury using a pneumatically driven piston. Effect of impact velocity on a 3mm deformation was assessed at 2.5m/sec (n=6), 3.0m/sec (n=6), 3.5m/sec (n=6), and no injury (n=6). After postoperative 24hours the rats were evaluated using several neurobehavioral tests including the rotarod test, beam-balance performance, and postural reflex test. Contusion volume and histopathologic findings were evaluated for each of the impact velocities. RESULTS: On the rotarod test, all the injured rats exhibited a significant difference compared to the sham-operated rats and increased velocity correlated with increased deficit (P<0.001). Contusion volume increased with increasing impact velocity. For the 2.5, 3.0, and 3.5m/sec groups, injured volumes were 18.8+/-2.3mm3, 26.8+/-3.1mm3, and 32.5+/-3.5mm3, respectively. In addition, neuronal loss in the hippocampal sub-region increased with increasing impact velocity. In the TUNEL staining, all the injured groups exhibited definitely positive cells at pericontusional area. However, there were no significant differences in the number of positive cells among the injured groups. CONCLUSION: Cortical impact velocity is a critical parameter in producing cortical contusion. Severity of cortical injury is proportional to increasing impact velocity of cortical injury.
Animals ; Brain Injuries ; Contusions ; In Situ Nick-End Labeling ; Neurons ; Rats ; Rats, Sprague-Dawley ; Reflex ; Rotarod Performance Test

OBJECTIVE: Focal brain ischemia induced in rats by occlusion of middle cerebral artery (MCA) is a widely used paradigm of human brain infarct. The purpose of this study is to establish chronic stroke model by MCA occlusion using intraluminal filament in rats. METHOD: A total 44 rats were operated by modified Longa's method. The surgical procedure consisted of introducing an intraluminal filament into the internal carotid artery and advancing it intracranially to block blood flow for 60 minutes into MCA. After this procedure motor and postural change were assessed using a 0~5 point grading scale consisted of forelimb, hindlimb and circling test. Behavioral tests such as rotarod, stepping and cylinder tests were examined in the survived rats after MCA occlusion up to 14 weeks post-ischemia. Autopsy was done to evaluate the cerebral infarct volume. RESULTS: Thirteen rats were survived up to 14 weeks post-ischemia and for the severely paralyzed subjects by acute neurological severity scoring were examined with behavioral tests once a week for 14 weeks. Although rotarod test have not shown any specific changes during 14 weeks, stepping and cylinder tests have shown stabilizing pattern since 4 weeks after the procedure. CONCLUSION: MCA occlusion using intraluminal filament could be reliable method to make stroke model in rats. We concluded that 4 weeks post-ischemia by this method in rats might be regarded as chronic model.
Animals ; Autopsy ; Brain ; Brain Ischemia ; Carotid Artery, Internal ; Forelimb ; Hindlimb ; Humans ; Middle Cerebral Artery ; Rats ; Rotarod Performance Test ; Stroke

OBJECTIVE: To investigate which outcome measurements are useful for detecting functional changes after therapeutic approach to delayed motor impairment in an animal model of Huntington's disease (HD). METHOD: R6/2 transgenic mice received intraventricular injections of adenoviral BDNF/noggin (AdB/N), AdBDNF, AdNull (n=15 each) at 4 weeks of age. Untreated R6/2s and wild-type mice were also recruited as controls. Motor performance was measured using rotarod analysis and locomotor activity test at regular intervals until preterminal age of 13 weeks. RESULTS: On constant speed rotarod testing, AdB/N-treated R6/2s exhibited a delayed disease progression after post- operative 6 weeks. AdB/N also ameliorated general locomotor activity deficits. One min-rotarod analysis showed a delayed motor impairment in AdBDNF group at preterminal age compared with AdNull and untreated controls, which was not shown in 3 min and 5 min-rotarod. Accelerating rotarod paradigm was not superior to constant speed. Partial therapeutic effects on locomotor activities were detected in total 60 min-monitoring, but not in 30 min- or 10 min- monitoring. CONCLUSION: Appropriate behavioral testing and outcome measurements should be selected to detect the treatment effect to slow functional deterioration in HD.
Animals* ; Disease Progression ; Huntington Disease* ; Injections, Intraventricular ; Mice ; Mice, Transgenic ; Models, Animal* ; Motor Activity ; Rotarod Performance Test

Industrial glues, known as 'Bonds' in Korea, contain many kinds of organic solvents, and glue sniffing of youths became one of the social problems in Korea. Mixed exposures to solvents by glue sniffing may induce chronic toxicities different from those by exposures to solvents of single component. To test effects of the glue sniffing on weight gain or central nervous system, two groups of 20 male Sprague-Dawley rats were exposed to air(control group) or vapors of the glues to narcotic status(exposed group), and weight check, tail flick test, hot plate test, rotarod treadmill test were done on the 14th, 24th, 36th, 45th, 53rd, 86th, 102nd, 117th, 134th and 151st days after the first exposure. On the 188th day, their brains were excised and examined by a pathologist. Weight gain, controlled against time change, showed significant difference between the groups, but response times in tail flick test, hot plate tests, and rotarod treadmill test didn't. In pathological examination with blind method, no macroscopic or microscopic difference were found between the two groups. These results suggests that organic lesion in central nervous system may not ensue glue sniffing, but, before firm conclusion, more studies in various exposure conditions should be followed.
Adhesives* ; Adolescent ; Animals ; Brain ; Central Nervous System* ; Exercise Test ; Humans ; Inhalant Abuse* ; Korea ; Male ; Rats* ; Rats, Sprague-Dawley ; Reaction Time ; Rotarod Performance Test ; Social Problems ; Solvents ; Weight Gain

BACKGROUND: The autophagy is the major route for lysosomal degradation of misfolded protein aggregates and oxidative cell components. We hypothesized that rapamycin (autophagy enhancer) would prolong the survival of motor neuron and suppress the disease progression in amyotrophic lateral sclerosis (ALS). METHODS: A total of 24 transgenic mice harboring the human G93A mutated SOD1 gene were used. The clinical status involving rotarod test and survival, and biochemical study of ALS mice model were evaluated. RESULTS: The onset of symptoms was significantly delayed in the rapamycin administration group compared with the control group. However, after the clinical symptom developed, the rapamycin exacerbated the disease progression and shortened the survival of ALS mice model, and apoptosis signals were up-regulated compared with control group. CONCLUSIONS: Even though further detailed studies on the relevancy between autophagy and ALS will be needed, our results revealed that the rapamycin administration was not effective for being novel promising therapeutic strategy in ALS transgenic mice and exacerbated the apoptosis.
Amyotrophic Lateral Sclerosis* ; Animals ; Apoptosis ; Autophagy ; Cellular Structures ; Disease Progression ; Humans ; Mice* ; Mice, Transgenic ; Motor Neurons ; Neuroprotective Agents* ; Rotarod Performance Test ; Sirolimus*

BACKGROUND: It is well known that anticonvusant drugs such as carbamazepine are effective in the management of various neuropathic pain conditions. Oxcarbazepine, a keto analogue of carbamazepine, might also be expected to have an analgesic effect because it is a derivative of carbamazepine. The aim of this study is to evaluate the analgesic effect of oxcarbazepine in a rat neuropathic pain model. METHODS: Male Sprague-Dawley rats were prepared by tightly ligating the L5 and L6 spinal nerves to reproduce neuropathic pain. Sixty neuropathic rats were randomly assigned into 6 groups for the intraperitoneal administration of drugs. Normal saline, vehicle (polyethylene glycol 400), oxcarbazepine (10 mg/kg, 20 mg/kg, 30 mg/kg and 50 mg/kg) were administered respectively to the individual groups. We examined mechanical and cold allodynia preadministration, and 15, 30, 60, 90, 120, 150 and 180 min after intraperitoneal drug administration. Mechanical allodynia was quantified by measuring the withdrawal frequency to stimuli with two von Frey filaments of 35.6 mN and 115.2 mN. Cold allodynia was quantified by measuring the frequency of foot lift to 100% acetone. Pain behavior may be influenced by the adverse effects of anticonvulsants, which include sedation, motor incoordination. We therefore measured the locomotor function of the neuropathic rats by using the rotarod test. RESULTS: The vehicle group showed no significant differences in the mechanical and cold allodynia versus the saline group. In the oxcarbazepine-treated groups, withdrawal frequencies to mechanical and cold stimuli were significantly reduced versus the pre-administration values and versus the vehicle group. The duration of antiallodynic effects increased dose-dependently, and these were maintained for 150 min at the highest dose. Only at the highest dose (50 mg/kg) did oxcarbazepine reduce the rotarod performance time. CONCLUSIONS: We conclude that oxcarbazepine reduces mechanical and cold allodynia in a rat neuropathic pain model and may be a candidate for the management of neuropathic pain.
Acetone ; Animals ; Anticonvulsants ; Ataxia ; Carbamazepine ; Foot ; Humans ; Hyperalgesia* ; Male ; Models, Animal* ; Neuralgia ; Rats* ; Rats, Sprague-Dawley ; Rotarod Performance Test ; Spinal Nerves

BACKGROUND: Intracerebral hemorrhage (ICH) is associated with a considerable proportion of stroke and head injuries, but except for supportive care, there is no medical therapy available. Transplantation of human neural stem cells (NSCs) can be used to reduce behavioral deficit in experimental ischemic infarct model. However, effect of stem cell transplantation in experimental intracerebral hemorrhage (ICH) is unknown. We hypothesized that NSCs could migrate and differentiate into neurons or glial cells, and improve functional outcome in ICH. METHODS: Experimental ICH was made by intrastriatal administration of bacterial collagenase in adult rats. Animals were randomized to receive intravenously either immortalized Lac-Z positive human NSCs (5x1 06 in 500microL, n=15) or same volume of saline (n=12) on the following day. Animals were evaluated for 8 weeks after surgery with behavioral test battery. After 8 weeks, animals were sacrificed and the brains were sectioned. Transplanted NSCs were detected by X-gal histochemistry or beta-gal immunohistochemistry, and differentiation of grafted NSCs were evaluated by double labeling of GFAP, NeuN, or neurofilament. RESULTS: Transplanted NSCs migrated to the side of peri-hematomal areas, and differentiated into neurons and astrocytes. NSCs injection group showed improved performances on rotarod test after 2 weeks and on limb placing test after 5 weeks compared with control group (p<0.05) and these effect persisted up to 8 weeks. CONCLUSIONS: Intravenously injected NSCs enter rat brain with ICH, and differentiate into astrocytes or neuronal cell, which lead to functional recovery. These findings show the possibility that NSCs can be used to reduce neurological deficits in the experimental ICH.
Adult ; Animals ; Astrocytes ; Brain ; Cerebral Hemorrhage* ; Collagenases ; Craniocerebral Trauma ; Extremities ; Humans* ; Immunohistochemistry ; Neural Stem Cells* ; Neuroglia ; Neurons ; Rats ; Rotarod Performance Test ; Stem Cell Transplantation ; Stroke ; Transplants

PURPOSE: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide. Severity of the initial insult is one of the most significant factors affecting outcome following TBI. In order to investigate the mechanisms of cellular injury and develop novel therapeutic strategies for TBI, we designed a standardized animal TBI model and evaluated histological and functional outcomes according to the degree of impact severity. METHODS: Male adult C57Bl/6 mice underwent controlled cortical impact (CCI) at varying depths of deflection (1.0-2.0 mm). We performed hematoxylin and eosin staining at 7 days after recovery from TBI. Neurobehavioral characterization after TBI was analyzed by the Barnes maze test, passive avoidance test, open field test, rotarod test, tail suspension test, and light/dark test. RESULTS: We observed a graded injury response according to the degree of deflection depths tested (diameter, 3 mm; velocity, 3 m/s; and duration, 500 ms) compared to sham controls. In the Barnes maze test, the severe TBI (2 mm depth) group showed reduced spatial memory as compared with the sham and mild TBI (1 mm depth) groups at 7 days after TBI. There was a significant difference in the results of the open field test and light/dark test among the three groups. CONCLUSION: Our findings demonstrate that the graded injury responses following TBI resulted in differential histopathological and behavioral outcomes in a mouse experimental CCI model. Thus, a model of CCI with histologic/behavioral outcome analysis may offer a reliable and convenient design for preclinical TBI research involving mice.
Adult* ; Animals ; Brain Injuries* ; Eosine Yellowish-(YS) ; Hematoxylin ; Hindlimb Suspension ; Humans ; Male ; Mice* ; Mortality ; Neurobehavioral Manifestations ; Rotarod Performance Test ; Spatial Memory