Fluid Percussion Injury Causes Loss of Forebrain Choline Acetyltransferase and Nerve Growth Factor Receptor Immunoreactive Cells in the Rat

Leonard, Jeffrey R.; Maris, Donald O.; Grady, M. Sean

doi:10.1089/neu.1994.11.379

Cited by 84 publications

(44 citation statements)

References 45 publications

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“…Although the possible mechanisms by which such cholinergic reductions may be mediated are numerous, reduced synthesis of ACh [27], altered release of ACh because of changes in ACh autoreceptor binding and signal transduction [16,28,29], or direct injury to cholinergic projections [29] are the most consistently observed effects of experimental injury.…”

Section: Cholinergic Dysfunction After Traumatic Brain Injury: Animalmentioning

confidence: 99%

The cholinergic hypothesis of cognitive impairment caused by traumatic brain injury

Arciniegas

2003

Curr Psychiatry Rep

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Cognitive impairments are among the most common neuropsychiatric sequelae of traumatic brain injury at all levels of severity. Cerebral cholinergic neurons and their ascending projections are particularly vulnerable to acute and chronic traumatically mediated dysfunction. In light of the important role of acetylcholine in arousal, attention, memory, and other aspects of cognition, cerebral cholinergic systems contribute to and may also be a target for pharmacologic remediation among individuals with post-traumatic cognitive impairments. This article will review the evidence in support of this hypothesis. Evidence of relatively selective damage to cholinergic injury, the development of persistent anticholinergic sensitivity, and the effects of cholinergic augmentation on memory performance are presented first. Thereafter, neuropathologic, electrophysiologic, and pharmacologic evidence of cholinergic dysfunction after traumatic brain injury in humans is reviewed. Finally, future directions for investigation of the cholinergic hypothesis and possible clinical applications of this information are discussed.

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Section: Cholinergic Dysfunction After Traumatic Brain Injury: Animalmentioning

confidence: 99%

The cholinergic hypothesis of cognitive impairment caused by traumatic brain injury

Arciniegas

2003

Curr Psychiatry Rep

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“…A time-dependent loss of ChAT enzymatic activity, the enzyme responsible for acetylcholine synthesis, and ChAT immunohistochemical staining have been reported after TBI (Donat et al, 2008;Gorman et al, 1996;Leonard et al, 1994;Schmidt and Grady, 1995;Sinson et al, 1997), and hypoxia (Row et al, 2007). Additionally, both 8-OH-DPAT and EE affect the cholinergic system (Barnes and Sharp, 1999;Paban et al, 2005;Torasdotter et al, 1998).…”

mentioning

confidence: 99%

Evaluation of a Combined Therapeutic Regimen of 8-OH-DPAT and Environmental Enrichment after Experimental Traumatic Brain Injury

Kline

McAloon²,

Henderson³

et al. 2010

Journal of Neurotrauma

126

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When provided individually, both the serotonin (5-HT 1A )-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and environmental enrichment (EE) enhance behavioral outcome and reduce histopathology after experimental traumatic brain injury (TBI). The aim of this study was to determine whether combining these therapies would yield greater benefit than either used alone. Anesthetized adult male rats received a cortical impact or sham injury and then were randomly assigned to enriched or standard (STD) housing, where either 8-OH-DPAT (0.1 mg/kg) or vehicle (1.0 mL/kg) was administered intraperitoneally once daily for 3 weeks. Motor and cognitive assessments were conducted on post-injury days 1-5 and 14-19, respectively. CA1/ CA3 neurons and choline acetyltransferase-positive (ChAT þ ) medial septal cells were quantified at 3 weeks. 8-OH-DPAT and EE attenuated CA3 and ChAT þ cell loss. Both therapies also enhanced motor recovery, acquisition of spatial learning, and memory retention, as verified by reduced times to traverse the beam and to locate an escape platform in the water maze, and a greater percentage of time spent searching in the target quadrant during a probe trial in the TBI þ STD þ 8-OH-DPAT, TBI þ EE þ 8-OH-DPAT, and TBI þ EE þ vehicle groups versus the TBI þ STD þ vehicle group ( p 0.0016). No statistical distinctions were revealed between the TBI þ EE þ 8-OH-DPAT and TBI þ EE þ vehicle groups in functional outcome or CA1/CA3 cell survival, but there were significantly more ChAT þ cells in the former ( p ¼ 0.003). These data suggest that a combined therapeutic regimen of 8-OH-DPAT and EE reduces TBI-induced ChAT þ cell loss, but does not enhance hippocampal cell survival or neurobehavioral performance beyond that of either treatment alone. The findings underscore the complexity of combinational therapies and of elucidating potential targets for TBI.

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“…NGF shows trophic activity in selected neuronal populations including motor-sensory neurons and cholinergic neurons in the basal nucleus of Meynert [91] and in the medial septum [92,93]. Since neurons in the medial septum are vulnerable in models of TBI [94], NGF represents an attractive candidate as a therapeutic tool after traumatic injury.…”

Section: Overviewmentioning

confidence: 99%

“…The septo-hippocampal pathway, crucial for memory retention and learning, has been shown to be damaged in models of experimental TBI including lateral fluid percussion (FP) [94][95][96][97] and controlled cortical impact (CCI) brain injury in rats [98,99]. Axonal injury may also compromise the retrograde transport of NGF to target areas.…”

Section: Alterations Of Ngf In Response To Tbimentioning

confidence: 99%

Neurotrophic Factors

Conte

Royo

Shimizu

et al. 2003

European Journal of Trauma

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Neurotrophic factors (NTFs) are endogenous molecules that play a crucial role in the maintenance, survival and differentiation of various neuronal populations within the developing and adult brain. In vitro and in vivo studies have shown that NTFs can attenuate neuronal injury initiated by cascades that are activated by traumatic brain injury (TBI) including excitotoxic damage, ischemia, and apoptosis. NTFs may also play a role in repair-regeneration processes such as axonal regeneration, neuronal plasticity and neurogenesis that could be critical for recovery after TBI. Nerve growth factor (NGF), insulin like growth factor I (IGF-I) and basic fibroblast growth factor (bFGF) and glial cell-derived neurotrophic factor (GDNF) have been shown to be effective in reducing neurobehavioral dysfunction and/or histopathological damage in experimental models of TBI. NTFs appear to be promising therapeutic tools for TBI, although more studies are necessary to elucidate their potential application and to test delivery systems that allow local, regulated supply to specific populations of neurons. This article provides an overview of the pathophysiology and potential therapeutic application of neurotrophic factors in TBI.

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Fluid Percussion Injury Causes Loss of Forebrain Choline Acetyltransferase and Nerve Growth Factor Receptor Immunoreactive Cells in the Rat

Cited by 84 publications

References 45 publications

The cholinergic hypothesis of cognitive impairment caused by traumatic brain injury

The cholinergic hypothesis of cognitive impairment caused by traumatic brain injury

Evaluation of a Combined Therapeutic Regimen of 8-OH-DPAT and Environmental Enrichment after Experimental Traumatic Brain Injury

Neurotrophic Factors

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