Concussion In Rats Research Articles

AH6809 decreases production of inflammatory mediators by PGE2 – EP2 – cAMP signaling pathway in an experimentally induced pure cerebral concussion in rats

Increasing evidence suggests that PGE2 metabolic pathway is involved in pathological changes of the secondary brain injury after traumatic brain injury. However, the underlying mechanisms, in particular, the correlation between various key enzymes and the brain injury, has remained to be fully explored. More specifically, it remains to be ascertained whether AH6809 (an EP2 receptor antagonist) would interfere with the downstream of the PGE2, regulate the inflammatory mediators and improve neuronal damage in the hippocampus by PGE2 – EP2 – cAMP signaling pathway. The expression and pathological changes of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), microsomal prostaglandin-E synthase-1 (mPGES-1), E-prostanoid receptor 2 (EP2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and inducible nitricoxide synthase (iNOS) in the CA1 area of hippocampus were evaluated by immunohistochemistry, Western blot and RT-PCR after pure cerebral concussion (PCC) induced by a metal pendulum closed brain injury in rats followed by AH6809 treatment. The morphology and number of neurons in CA1 region were analyzed by cresyl violet staining. The concentration of prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) was assayed by ELISA. Many neurons in hippocampal CA1 area appeared to undergo necrosis and the number of neurons was concomitantly reduced after PCC injury. With the passage of time, the protein and mRNA expression of various key enzymes including COX-1, COX-2 and mPGES-1, EP2 receptor, and inflammatory mediators including TNF-α, IL-1β and iNOS was increased; meanwhile, the concentration of PGE2 and cAMP was enhanced. After PCC injury given AH6809 intervention, injury of neurons in hippocampal CA1 area was attenuated. The protein and mRNA expression of COX-1, COX-2, mPGES-1, EP2, TNF-α, IL-1β and iNOS was decreased, this was coupled with reduction of PGE2 and cAMP. The results suggest that PGE2 metabolic pathway is involved in secondary pathological changes of PCC. AH6809 improves the recovery of injured neurons in the hippocampal CA1 area and downregulates the inflammatory mediators by PGE2 – EP2 – cAMP signaling pathway.

Air-puff induced vocalizations: A novel approach to detecting negative affective state following concussion in rats

BackgroundNegative emotional states resulting from concussion are of increasing concern. In the current study, we developed a model to investigate negative affect following concussion in the projectile concussive impact (PCI) model. High frequency ultrasonic vocalizations (22kHz USVs) are associated with negative affective stimuli in rats. Changes in negative affective state were examined following PCI using a mild air-puff stimulus to elicit 22kHz USVs. New methodForty-eight hours post-injury, animals were placed into a clean acrylic box lined with bedding. A 5min baseline recording was followed by 15 air puffs (55psi) spaced 15s apart aimed at the upper back and neck. ResultsInjured animals produced on average 153.5±55.13 more vocalizations than shams, vocalizing on average 4min longer than shams. Additionally, concussed animals vocalized to fewer air-puffs, exhibiting a 1.5 fold lower threshold for the expression of negative affect. Comparison with existing methodsStudies currently used to test negative affective states following concussion in animals, such as the elevated plus maze and forced swim task have, as of yet, been unsuccessful in demonstrating injury effects in the PCI model. While the air-puff test has been applied in other fields, to our knowledge it has not been utilized to study traumatic brain injury. ConclusionThe current study demonstrates that the air-puff vocalization test may be a valuable tool in assessing negative mood states following concussion in rat models and may be used to evaluate novel therapies following brain injury for the treatment of mood dysfunction.

Prediction of Post-Concussive Behavioral Changes in a Rodent Model Based on Head Rotational Acceleration Characteristics.

Quantifying injury tolerance for concussion is complicated by variability in the type, severity, and time course of post-injury physiological and behavioral changes. The current study outlined acute and chronic changes in behavioral metrics following rotational acceleration-induced concussion in rats. The Medical College of Wisconsin (MCW) rotational injury model independently controlled magnitude and duration of the rotational acceleration pulse. Increasing rotational acceleration magnitude produced longer recovery times, which were used in this study and our prior work as an assessment of acute injury severity. However, longer duration rotational accelerations produced changes in emotionality as measured using the elevated plus maze. Cognitive deficits were for the most part not apparent in the Morris water maze assessment, possibly due to the lower severity of rotational acceleration pulses incorporated in this study. Changes in emotionality evolved between acute and chronic assessments, in some cases increasing in severity and in others reversing polarity. These findings highlight the complexity of quantifying injury tolerance for concussion and demonstrate a need to incorporate rotational acceleration magnitude and duration in proposed injury tolerance metrics. Rotational velocity on its own was not a strong predictor of the magnitude or type of acute behavioral changes following concussion, although its combination with rotational acceleration magnitude using multivariate analysis was the strongest predictor for acute recovery time and some chronic emotional-type behavioral changes.

Neuroscience 2014 Showcases Advances in Mental Health Research

Knowledge about structure, development, health, and diseases of the brain and nervous system is advancing rapidly, according to research by some of the world’s leading neuroscientists.

Diet, age, and prior injury status differentially alter behavioral outcomes following concussion in rats

Mild traumatic brain injury (mTBI) or concussion affects a large portion of the population and although many of these individuals recover completely, a small subset of people experience lingering symptomology and poor outcomes. Little is known about the factors that affect individual susceptibility or resilience to poor outcomes after mTBI and there are currently no biomarkers to delineate mTBI diagnosis or prognosis. Based upon the growing literature associated with caloric intake and altered neurological aging and the ambiguous link between repetitive mTBI and progressive neurodegeneration, the current study was designed to examine the effect of a high fat diet (HFD), developmental age, and repetitive mTBI on behavioral outcomes following a mTBI. In addition, telomere length was examined before and after experimental mTBI. Sprague Dawley rats were maintained on a HFD or standard rat chow throughout life (including the prenatal period) and then experienced an mTBI/concussion at P30, P30 and P60, or only at P60. Behavioral outcomes were examined using a test battery that was administered between P61–P80 and included; beam-walking, open field, elevated plus maze, novel context mismatch, Morris water task, and forced swim task. Animals with a P30 mTBI often demonstrated lingering symptomology that was still present during testing at P80. Injuries at P30 and P60 rarely produced cumulative effects, and in some tests (i.e. beam walking), the first injury may have protected the brain from the second injury. Exposure to the high fat diet exacerbated many of the behavioral deficits associated with concussion. Finally, telomere length was shortened following mTBI and was influenced by the animal's dietary intake. Diet, age at the time of injury, and the number of prior concussion incidents differentially contribute to behavioral deficits and may help explain individual variations in susceptibility and resilience to poor outcomes following an mTBI.

A study on the cognitive function after complicate cerebral concussion in rats

Objective To study the spatial cognition of rats with different types of cerebral concussion (CC) in rats. Methods Animal model of cerebral concussion were duplicated in SD rats using a metallic pendulum striker concussive device. According to there were any other intracranial injury or not, the cerebral concussion (CC) had been classified into two types, that was, pure cerebral concussion ( PCC) and complicate cerebral concussion ( CCC) . The injured rats were randomly divided into CCC 1, 2 and 3 weeks sub-group and each group had 10 animals,one control group was used. Learning and memory ability were assessed with Morris water maze. The data were processed by SPSS 11.5. Results Comparsion with cotrol group the performance latency in CCC prolonged (108.92 ± 11.82)s, (90.94 ± 20.09) s, (70.79 s ± 21.71) s, (82.92 ± 26.98) s, (68.89 ± 39.13) s, (37.26 ±37.61)s, (44.76 ± 24.01) s, (32.98 ±18.75 ) s and shown statistics significance (F = 3.514, P< 0.05 ) up to 6 days and 10~(th)～ 11~(th) day post injury. Conclusion There are severe cognitive deficits associated with intracranid injury in focal cerebral occussion in rats. Key words: Rats; Cerebral concussion; Spatial cognitive deficits; Morris water maze

Study on vestibulomotor function and cognitive deficits induced by multiple cerebral concussion in rats

目的 探讨多重脑震荡(Multiple cerebral concussion,MCC)对大鼠平衡运动与认知功能的影响,并为二次冲击综合征(SIS)的临床诊断与治疗提供理论依据.方法 采用自制金属单摆式闭合性脑损伤装置复制三重的MCC大鼠模型;应用平衡木实验(BBT)及噪音横杆跑动实验(BWT)于伤后1～10d对MCC大鼠平衡运动与认知功能进行评价;运用SPSS11.5统计软件包分析测试结果.结果 与对照组(60.00±0.00)s比较,MCC组大鼠在伤后第1天平衡时间明显缩短至(54.50±13.89)s,差异具有显著性(P＜0.05),第2天开始恢复,至第4天恢复正常.BWT结果显示伤后第1天步入潜伏期明显延长,第2天开始恢复,至第10天尚未完全恢复正常,分别为:(20.54±21.89)s、(14.34±18.71)s、(14.50±20.76)s、(13.84±18.99)s、(9.48±15.51)s、(4.99±2.45)s、(5.98±7.28)s、(4.38±2.98)s、(5.60±9.28)s和(6.74±10.75)s.除第9天外,其他各时间点与对照组相比,差异均具有显著性(P＜0.05).BWT评分结果 显示伤后第1～3天评分均显著低于对照组,分别为(4.07±1.91)s、(4.37±1.65)s和(4.37±1.65)s.结论 MCC大鼠存在不同程度的平衡运动与认知功能障碍,平衡功能恢复快,协调运动与认知功能恢复较慢。

A study on the spatial learning and memory ability after brain concussion in rats

目的 探讨脑震荡后不同时期水迷宫空间学习记忆功能的变化.方法 成年SD大鼠48只,应用自制单摆式脑损伤机械打击装置建立单纯性脑震荡大鼠模型,符合损伤判断标准之大鼠随机分为伤后1周、2周、3周组和对照组;应用Morris水迷宫(MWM)实验,评价大鼠PBC后1周、2周和3周空间学习记忆功能.结果 与对照组相比,受伤大鼠在MWM水下平台试验中,PBC后1～7d的前3 d,找到平台的时间显著延长,分别为(95.36±19.85)s、(71.09±29.41)s、(67.21±31.73)s,而在伤后8～21 d差异无显著性.在MWM探测试验中,各组大鼠在原有平台象限(第3象限)停留的时间差异无显著性.结论 单纯性脑震荡大鼠在伤后早期出现空间学习记忆功能障碍。

Assessment of sensorimotor and cognitive deficits induced by the cerebral concussion in rats

目的 运用平衡木及噪音横杆跑动试验对大鼠单纯性脑震荡(Pure Cerebral Concussion,PCC)和复杂性脑震荡(Complicated Cerebral Concussion,CCC)后的平衡功能及学习记忆功能的影响进行评估.方法采用大鼠金属单摆脑损伤复制仪和判断标准,制备单纯性脑震荡和复杂性大鼠脑震荡模型,应用平衡木及噪音横杆跑动试验测试其平衡时间以及步入黑箱的潜伏期;运用SPSS软件包分析测试成绩.结果PCC组平衡时间与对照组比较差异无显著性;但在横杆跳动实验(BWT)中,仅在1,2d步入潜伏期显著延长为(29.50±25.30)s和(30.52±26.42)s.CCC组平衡时间与对照组比较,在伤后第1～3天有明显差异,分别为:(38.35±23.48)s,(41.63±19.24)s和(44.76±21.85)s;在BWT中,第1～5天步入潜伏期均显著延长,逐渐从(48.12±18.24)s恢复至(27.10±28.36)s.结论在脑震荡后PCC组和CCC组均有不同程度的平衡、运动学习功能障碍.PCC组在伤后损伤程度较轻、恢复快;CCC组在伤后损伤程度较重、恢复较慢。

Delayed changes in regional brain energy metabolism following cerebral concussion in rats.

Traumatic brain injury (TBI) results in an acute altered metabolic profile of brain tissue which resolves within hours of initial insult and yet some of the functional deficits and cellular perturbations persist for days. It is hypothesized that a delayed change in energy status does occur and is a factor in the neural tissue's ability to survive and regain function. Regional metabolic profile and glucose consumption were determined at either 1 or 3 days following two different intensities of parasagittal fluid-percussion (F-P). A significant decrease in both 1CMRgluc and levels of ATP and P-creatine was evident in the hemisphere ipsilateral to the trauma at 1 day after the insult. The effect was greater in the cortical than the subcortical regions and was more pronounced at the higher trauma intensity. Normalization of glucose consumption and energy levels was essentially complete by 3 days. It would appear that the delayed metabolic changes at 1 day postinsult cannot be explained by a secondary ischemia since the changes in the metabolite profile do not elicit an increase in the consumption of glucose. These changes in energy metabolites may account for and contribute to the chronic neurological deficits following TBI.

Treatment of pediatric traumatic brain injury: A broad path to a narrow gate

Treatment of pediatric traumatic brain injury: A broad path to a narrow gate

Concussion-induced retrograde amnesia in rats

Three experiments were conducted to investigate the characteristics of retrograde amnesia (RA) induced by concussion in rats. In Experiment 1, rats receiving experimental concussion shortly after training in a single punishment trial exhibited severe forgetting on a retention test 48 h later. In the second experiment, rats receiving a concussion within 6 h after training showed severe RA, while those receiving concussion one day to five days after training exhibited progressively weaker amnesia. In Experiment 3, amnesic animals in one group received pretest noncontingent foot shock as a reminder treatment. This pretest cue significantly increased the cross-through latency, thus indicating a reduction in the memory deficit resulting from concussion. These results suggest that experimental concussion can be an effective method to induce retrograde memory loss in rats; that the RA caused by concussion is time-dependent; and that concussion-induced RA can be alleviated by a pretest cue,indicating that the underlying mechanism of concussion-induced RA is more likely to be a retrieval deficit than a consolidation failure.

Dynamic changes in local cerebral glucose utilization following cerebral concussion in rats: evidence of a hyper- and subsequent hypometabolic state

Following cerebral concussion, in which there is no evidence of direct morphological damage, cells are exposed to an increase in extracellular potassium as well as an accumulation of calcium. This concussion-induced ionic flux most likely alters the cellular energy demands thereby modifying metabolic processes. To investigate the metabolic changes after cerebral concussion, local cerebral metabolic rates for glucose (lCMRglc) utilizing [ 14C]2-deoxy- d-glucose were studied in rats(n=98; 250–300g) immediately, 30 min, 6 h, 1, 2, 3, 5 and 10 days following a unilateral fronttoparietal fluid percussion (F-P) injury (3.7–4.3 atm). Compared to sham controls, animals exhibited bilateral hypermetabolism immediately following brain injury. However, this effect was more pronounced in structures ipsilateral to the site of F-P and was especially marked for the cerebral cortex (46.6–30.1% higher than control) and hippocampus (90.1–84.4% higher than control). By 30 min post-trauma many ipsilateral regions still showed evidence of hypermetabolism, although their lCMRglc had subsided. Beginning as early as 6 h following injury many regions within the ipsilateral cortex and hippocampus went into a state of metabolic depression (16.4–33.7% of control) which lasted for as long as 5 days. These results indicate that, although not mechanically damaged from the insult, cells exposed to concussive injury dramatically alter their metabolic functioning. This period of post-concussive metabolic dysfunction may delineate a period of time, following injury, during which cells are functionally compromised.

Concussion in rats causes an immediate change in occupancy but not affinity of hypothalamic cholinergic receptors

Experimental concussion in rats is associated with subsequent enhanced binding in vitro of certain ligands to hypothalamic tissue but not to other brain regions. Scatchard analysis shows that the number of specific binding sites for [ 3H]quinuclidinylbenzilate increases within 3 s after concussion with no significant change in binding affinity. The apparent increase in receptors is likely the result of a deficit in binding of endogenous ligand. We propose that concussion produces a pressure wave that deforms cholinergic and possibly other receptors selectively in the hypothalamus, resulting in a transient deficit in transmitter binding and interruption of neuronal circuits concerned with the state of consciousness.

Cerebral concussion in rats rapidly induces hypothalamic-specific effects on opiate and cholinergic receptors

Conscious male adult rats were concussed by a blow to the occiput with a blunt dart, shot from a spring-loaded pistol. Animals were decapitated within 2 sec, brains quickly removed, several brain regions homogenized in cold buffer and radioreceptor assays carried out. There was a 20% increase in binding of [3H]naloxone and [3H]QNB in the hypothalamus but not in the amygdala, striatum, hippocampus, cortex, midbrain and hindbrain. For animals killed 5-10 sec after concussion, when normal conscious behavior had returned, there were no changes in binding between control and concussed rats. Binding of [3H]spiroperidol and [3H]ouabain was unaffected by concussion. To rule out changes due to non-specific stress, one series of rats received a blow to the lower body. There was no change from control in [3H]QNB binding to hypothalamic tissues by a body blow as compared with the blow to the head. The findings suggests decreased binding of endogenous endorphins and acetylcholine to their respective receptors as a result of concussion. The transient deficit in endogenous transmitter binding may temporarily interrupt hypothalamic circuits concerned with the state of consciousness.