Exploratory, cognitive, and depressive-like behaviors in adult and pediatric mice exposed to controlled cortical impact

OBJECTIVE: Sequelae of behavioral impairments associated with human traumatic brain injury (TBI) include neurobehavioral problems. We compared exploratory, cognitive, and depressive-like behaviors in pediatric and adult male mice exposed to controlled cortical impact (CCI).METHODS: Pediatric (21 to 25 days old) and adult (8 to 12 weeks old) male C57Bl/6 mice underwent CCI at a 2-mm depth of deflection. Hematoxylin and eosin staining was performed 3 to 7 days after recovery from CCI, and injury volume was analyzed using ImageJ. Neurobehavioral characterization after CCI was performed using the Barnes maze test (BMT), passive avoidance test, open-field test, light/dark test, tail suspension test, and rotarod test. Acutely and subacutely (3 and 7 days after CCI, respectively), CCI mice showed graded injury compared to sham mice for all analyzed deflection depths.RESULTS: Time-dependent differences in injury volume were noted between 3 and 7 days following 2-mm TBI in adult mice. In the BMT, 2-mm TBI adults showed spatial memory deficits compared to sham adults (P < 0.05). However, no difference in spatial learning and memory was found between sham and 2-mm CCI groups among pediatric mice. The open-field test, light/dark test, and tail suspension test did not reveal differences in anxiety-like behaviors in both age groups.CONCLUSION: Our findings revealed a graded injury response in both age groups. The BMT was an efficient cognitive test for assessing spatial/non-spatial learning following CCI in adult mice; however, spatial learning impairments in pediatric mice could not be assessed.

Modeling Traumatic Brain Injury Rats with Controlled Cortical Impact: Coma and Cognitive Dysfunction / 中国康复理论与实践

@#Objective To establish the model of traumatic brain injury in rats with controlled cortical impact (CCI), and investigate the features of coma and cognition. Methods 40 male Sprague-Dawley rats were randomly divided into control group (n=10), sham group (n= 10) and CCI group (n=20). CCI group was impacted at bilateral frontal lobe with the velocity of 3.5 m/s, depth of 7 mm and dwell time of 250 ms. The time of consciousness loss was recorded, and all the rats were investigated with Morris Water Maze 10 and 20 days after operation. Results The time of consciousness loss was longer in the CCI group than in the control group and the sham group (P<0.001). The escape latency was longer in the CCI group than in the control group and the sham group (P<0.001), while the percent of time spend in goal quarter during probe trial was less (P<0.001), both 10 days and 20 days after operation. Conclusion CCI at bilateral frontal lobe of rats can establish the model of severe traumatic brain injury with coma and long-term cognitive dysfunction.

Modeling Traumatic Brain Injury Rats with Controlled Cortical Impact:Coma and Cognitive Dysfunction / 中国康复理论与实践

Objective To establish the model of traumatic brain injury in rats with controlled cortical impact (CCI), and investigate the features of coma and cognition. Methods 40 male Sprague-Dawley rats were randomly divided into control group (n=10), sham group (n=10) and CCI group (n=20). CCI group was impacted at bilateral frontal lobe with the velocity of 3.5 m/s, depth of 7 mm and dwell time of 250 ms. The time of consciousness loss was recorded, and all the rats were investigated with Morris Water Maze 10 and 20 days after opera-tion. Results The time of consciousness loss was longer in the CCI group than in the control group and the sham group (P<0.001). The es-cape latency was longer in the CCI group than in the control group and the sham group (P<0.001), while the percent of time spend in goal quarter during probe trial was less (P<0.001), both 10 days and 20 days after operation. Conclusion CCI at bilateral frontal lobe of rats can establish the model of severe traumatic brain injury with coma and long-term cognitive dysfunction.

The establishment of the controlled cortical impact-induced traumatic brain injury model with different severity in rats / 中华行为医学与脑科学杂志

Objective To establish the electric controlled cortical impact (eCCI)-induced traumatic brain injury (TBI) model in rats with different severity in degree,which may serve as a suitable platform to provide experimental evidence for the pathophysiological following TBI.Methods A total of 40 male Wistar rats were randomly divided into 3 experimental groups and sham group.TBI rats (n=10/group) were positioned beneath the controlled cortical impactor device (eCCI) and subjected to impact injury at 2 mm depth of penetration,for a sustained depression of 200 ms,at 4 m/s,5 m/s,6 m/s velocity for mild,moderate,and severe TBI,respectively.Sham-operated rats (n=10) underwent identical surgical procedures,including craniotomy,without receiving the cortical impact.Neurological function and regional cerebral flow (24 h after CCI),contusion volume,histopathological,and ultrastructural changes (48 h after CCI) were measured,respectively.Results The severity of the pathological changes in rats was increased as the injury aggravated.The eCCI device impacted the brain at 4 m/s,5 m/s,6 m/s velocity for mild,moderate,and severe TBI,respectively.TBI groups showed impaired neurological function,and decreased rCBF lower than that of sham-operated group (all P＜0.01).Furthermore,neuronal pathological abnormalities in TBI groups,including neuron shrinking,perineuronal vacuole,and structural abnormalities of mitochondria.Increased severity of injury was apparent following the increased level of the impacted velocity,and significant differences were observed between TBI groups (P＜0.05).Conclusion The TBI animal model with mild,moderate,and severe brain injury can be established successfully by 4 m/s,5 m/s,and 6 m/s of impact velocity respectively with the eCCI-6.3 device.The novel eCCI-induced TBI model in rats possibly serves as a novel useful approach in the development of TBI models.

Effect on Varying the Impact Velocity in the Controlled Cortical Impact Injury Model: Injury Severity and Impact Velocity

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.