Prolonged memory impairment in the absence of hippocampal cell death following traumatic brain injury in the rat

Lyeth, Bruce G.; Jenkins, Larry W.; Hamm, Robert J.; Dixon, C. Edward; Phillips, Linda R.; Clifton, Guy L.; Young, Harold F.; Hayes, Ronald L.

doi:10.1016/0006-8993(90)91229-a

Cited by 401 publications

(213 citation statements)

References 35 publications

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“…In the laboratory, the Morris water maze (MWM) and radial arm maze routinely demonstrate injury-related cognitive deficits [37,54,63,67]. However, contextual fear response minimizes the impact of motor deficits and motivation [37,46,66].…”

Section: Discussionmentioning

confidence: 99%

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

Lifshitz

Witgen

Grady

2007

Behavioural Brain Research

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Conditioned fear associates a contextual environment and cue stimulus to a foot shock in a single training trial, where fear expressed to the trained context or cue indicates cognitive performance. Lesion, aspiration or inactivation of the hippocampus and amygdala impair conditioned fear to the trained context and cue, respectively. Moreover, only bilateral experimental manipulations, in contrast to unilateral, abolish cognitive performance.In a model of unilateral brain injury, we sought to test whether a single lateral fluid percussion brain injury impairs cognitive performance in conditioned fear. Brain-injured mice were evaluated for anterograde cognitive deficits, with the hypothesis that acute injury-induced impairments improve over time. Male C57BL/6J mice were brain-injured, trained at five or 27 days post-injury, and tested 48 hours later for recall of the association between the conditioned stimuli (trained context or cue) and the unconditioned stimulus (foot shock) by quantifying fear-associated freezing behavior. A significant anterograde hippocampal-dependent cognitive deficit was observed at seven days in brain-injured compared to sham. Cued fear conditioning could not detect amygdala-dependent cognitive deficits after injury and stereological estimation of amygdala neuron number corroborated this finding. The absence of injury-related freezing in a novel context substantiated injury-induced hippocampal-dependent cognitive dysfunction, rather than generalized fear. Variations in the training and testing paradigms demonstrated a cognitive deficit in consolidation, rather than acquisition or recall. By one month post-injury, cognitive function recovered in brain-injured mice. Hence, the acute injury-induced cognitive impairment may persist while transient pathophysiological sequelae are underway, and improve as global dysfunction subsides.

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Section: Discussionmentioning

confidence: 99%

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

Lifshitz

Witgen

Grady

2007

Behavioural Brain Research

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“…First, TBI produces an increased and se lective vulnerability of the hippocampus to second ary ischemic insult (Jenkins et aI., 1989). Second, TBI causes persistent deficits in spatial memory performance tasks that are dependent on intact hip pocampal function (Dixon et aI., 1987;Lyeth et al , 1990). Finally, TBI alters hippocampal receptor binding (Miller et aI., 1991) and impairs hippocam pal long-term potentiation induction (Miyazaki et aI., 1992) post injury.…”

Section: Discussionmentioning

confidence: 99%

Hypothermia Attenuates the Loss of Hippocampal Microtubule-Associated Protein 2 (MAP2) following Traumatic Brain Injury

Taft

Yang

Dixon

et al. 1993

J Cereb Blood Flow Metab

102

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Summary: Traumatic brain injury (TBI) produces a tis sue-specific decrease in protein levels of microtubule associated protein 2 (MAP2), an important cross-linking component of the neuronal cytoskeleton. Because mod erate brain hypothermia (30°C) reduces certain neurobe havioral deficits produced by TBI, we examined the effi cacy of moderate hypothermia (30°C) in reversing the TBI-induced loss of MAP2 protein. Naive, sham-injured, and moderate (2.1 atm) fluid percussion-injured rats were assessed for MAP2 protein content 3 h post injury using quantitative immunoreactivity measurements. Parallel groups of sham-injured and fluid percussion-injured ani mals were maintained in moderate hypothermia (30°C), as measured by temporalis muscle temperature, for MAP2 quantitation 3 h post injury. No difference in MAP21eveisModerate hypothermia has proven to be an effec tive strategy in the laboratory for protection of neu rons and neuronal function following CNS injury. Early clinical studies employing moderate whole body hypothermia in patients with stroke and brain injury were abandoned due to lack of standardized laboratory models for study and absence of con trolled trial methodologies. Recent studies employ ing moderate levels of hypothermia have shown ef ficacy in prevention of histological cell loss and diminution of neurological function following global and focal ischemia in rats (Busto et aI., 1987(Busto et aI., , 1989 and gerbils (Clifton et aI., 1989 796was observed between naive and sham-iI1iured normo thermic animals. Hypothermia alone had no effect on sol uble MAP2 levels in sham-injured animals compared with normothermic sham-injured controls (88.0 ± 7.3%; p > 0.10). Fluid percussion injury dramatically reduced MAP21eveis in he normothermic group (44.3 ± 5.9%; p < 0.0005) compared with normothermic sham-injured con trols. No significant reduction of MAP2 was seen in the hypothermic injured group (95.2 ± 4.6%; compared with hypothermic sham-injured controls, p > 0.20). Although it is premature to infer any causal link, the data suggest that the attenuation of injury-induced MAP2 loss by hy pothermia may contribute to its overall neuroprotective action.

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“…Knockdown of the NMDA-type glutamate receptor 1 in a mere 6% to 7% of CA1 neurons in the hippocampus is enough to significantly impair memory formation (Cheli et al, 2006). The FPI model, without any accompanying hypoxia, does not result in substantial neuronal loss throughout the hippocampus with the exception of the CA3 and hilar subregions, but does result in significant hippocampal-dependent memory impairments (Lyeth et al, 1990;Carbonell et al, 1998;Grady et al, 2003). Accordingly, hippocampal LTP is impaired and subtle structural damage is seen in the hippocampus after TBI (Sanders et al, 2000;Golarai et al, 2001;Scheff et al, 2005).…”

Section: Figurementioning

confidence: 99%

Alterations in Mammalian Target of Rapamycin Signaling Pathways after Traumatic Brain Injury

Chen

Atkins

Liu

et al. 2006

J Cereb Blood Flow Metab

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In response to traumatic brain injury (TBI), neurons initiate neuroplastic processes through the activation of intracellular signaling pathways. However, the molecular mechanisms underlying neuroplasticity after TBI are poorly understood. To study this, we utilized the fluid-percussion brain injury (FPI) model to investigate alterations in the mammalian target of rapamycin (mTOR) signaling pathways in response to TBI. Mammalian target of rapamycin stimulates mRNA translation through phosphorylation of eukaryotic initiation factor 4E binding protein-1 (4E-BP1), p70 ribosomal S6 kinase (p70S6K), and ribosomal protein S6 (rpS6). These pathways coordinate cell growth and neuroplasticity via dendritic protein synthesis. Rats received sham surgery or moderate parasagittal FPI on the right side of the parietal cortex, followed by 15 mins, 30 mins, 4 h, 24 h, or 72 h of recovery. Using Western blot analysis, we found that mTOR, p70S6K, rpS6, and 4E-BP1 phosphorylation levels were significantly increased in the ipsilateral parietal cortex and hippocampus from 30 mins to 24 h after TBI, whereas total protein levels were unchanged. Using confocal microscopy to localize these changes, we found that rpS6 phosphorylation was increased in the parietal cortex and all subregions of the hippocampus. In accordance with these results, eIF4E, a key, rate-limiting mRNA translation factor, was also phosphorylated by mitogen-activated protein kinase-interacting kinase 1 (Mnk1) 15 mins after TBI. Together, these results suggest that changes in mRNA translation may be one mechanism that neurons use to respond to trauma and may contribute to the neuroplastic changes observed after TBI.

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Prolonged memory impairment in the absence of hippocampal cell death following traumatic brain injury in the rat

Cited by 401 publications

References 35 publications

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

Hypothermia Attenuates the Loss of Hippocampal Microtubule-Associated Protein 2 (MAP2) following Traumatic Brain Injury

Alterations in Mammalian Target of Rapamycin Signaling Pathways after Traumatic Brain Injury

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