The Effectiveness of Donepezil for Cognitive Rehabilitation After Traumatic Brain Injury

Ballesteros, Javier; Güemes, Itziar; Ibarra, Nora; Quemada, José Ignacio

doi:10.1097/01.htr.0000319935.99837.96

Cited by 42 publications

(26 citation statements)

References 20 publications

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“…This has, in part, been shown to be the case in TBI too. Donepezil a U.S. Food and Drug Administration (FDA) approved anticholinesterase for the treatment of AD has been found to be moderately beneficial in improving memory deficits in several clinical studies and in some, but not all, experimental models of TBI (Taverni et al, 1998; Whelan et al, 2000; Masanic et al, 2001; Balesteros et al, 2008; Fujiki et al, 2008; Shaw et al, 2013; Yu et al, 2015). The N-methyl-d-aspartate antagonist memantine, a further FDA-approved drug for the symptomatic treatment of AD, has similarly been shown to be neuroprotective and to possess anti-lipid peroxidation properties in several preclinical studies involving experimentally induced TBI in rodents (Rao et al, 2001; Ozsuer et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Mild traumatic brain injury-induced hippocampal gene expressions: The identification of target cellular processes for drug development

Tweedie

Rachmany

Kim

et al. 2016

Journal of Neuroscience Methods

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Background Neurological dysfunction after traumatic brain injury (TBI) poses short-term or long-lasting health issues for family members and health care providers. Presently there are no approved medicines to treat TBI. Epidemiological evidence suggests that TBI may cause neurodegenerative disease later in life. In an effort to illuminate target cellular processes for drug development, we examined the effects of a mild TBI on hippocampal gene expression in mouse. Methods mTBI was induced in a closed head, weight drop-system in mice (ICR). Animals were anesthetized and subjected to mTBI (30 g). Fourteen days after injury the ipsilateral hippocampus was utilized for cDNA gene array studies. mTBI animals were compared with sham-operated animals. Genes regulated by TBI were identified to define TBI-induced physiological/pathological processes. mTBI regulated genes were divided into functional groupings to provide gene ontologies. Genes were further divided to identify molecular/cellular pathways regulated by mTBI. Results Numerous genes were regulated after a single mTBI event that mapped to many ontologies and molecular pathways related to inflammation and neurological physiology/pathology, including neurodegenerative disease. Conclusions These data illustrate diverse transcriptional changes in hippocampal tissues triggered by a single mild injury. The systematic analysis of individual genes that lead to the identification of functional categories, such as gene ontologies and then molecular pathways, illustrate target processes of relevance to TBI pathology. These processes may be further dissected to identify key factors that can be evaluated at the protein level to highlight possible treatments for TBI in human disease and potential biomarkers of neurodegenerative processes.

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Section: Discussionmentioning

confidence: 99%

Mild traumatic brain injury-induced hippocampal gene expressions: The identification of target cellular processes for drug development

Tweedie

Rachmany

Kim

et al. 2016

Journal of Neuroscience Methods

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“…Altogether these results suggest that the interaction between cholinergic and histaminergic systems is more complex than previously thought and further experiments are required to fully understand its mechanism and physiological implications. Donepezil is currently used in clinics to treat mild cognitive deficits observed in Alzheimer's disease patients (Cummings et al, 2013) and has been proposed for the rehabilitation of cognitive impairments after traumatic brain injuries (Ballesteros et al, 2008).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Donepezil, an acetylcholine esterase inhibitor, and ABT-239, a histamine H3 receptor antagonist/inverse agonist, require the integrity of brain histamine system to exert biochemical and procognitive effects in the mouse

et al. 2016

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“…15,16 Among them, acetylcholinesterase inhibitors (AChEIs), which extend the effect of ACh on neurons and restore cholinergic tone, have received the most attention. [12][13][14][15] AChEIs have shown improvement in memory and executive function in TBI patients [17][18][19][20][21][22][23] and mixed results in rodents. 24,25 For example, donepezil, a mixed competitive, reversible, and potent AChEI, exhibits small-to-moderate pro-cognitive effects in humans 23 and in select laboratory conditions.…”

Section: Introductionmentioning

confidence: 99%

“…[12][13][14][15] AChEIs have shown improvement in memory and executive function in TBI patients [17][18][19][20][21][22][23] and mixed results in rodents. 24,25 For example, donepezil, a mixed competitive, reversible, and potent AChEI, exhibits small-to-moderate pro-cognitive effects in humans 23 and in select laboratory conditions. [24][25][26][27][28] In a murine model of cortical impact injury, donepezil was reported to improve spatial learning 24 , however, the effect was modest and the post-hoc statistic did not correct for multiple comparisons, which may have affected the interpretation.…”

Section: Introductionmentioning

confidence: 99%

Galantamine and Environmental Enrichment Enhance Cognitive Recovery after Experimental Traumatic Brain Injury But Do Not Confer Additional Benefits When Combined

Tremblaye

Bondi

Lajud

et al. 2017

Journal of Neurotrauma

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Environmental enrichment (EE) enhances cognition after traumatic brain injury (TBI). Galantamine (GAL) is an acetylcholinesterase inhibitor that also may promote benefits. Hence, the aims of this study were to assess the efficacy of GAL alone (standard [STD] housing) and in combination with EE in adult male rats after TBI. The hypothesis was that both therapies would confer motor, cognitive, and histological benefits when provided singly, but that their combination would be more efficacious. Anesthetized rats received a controlled cortical impact or sham injury, then were randomly assigned to receive GAL (1, 2, or 3 mg/kg; intraperitoneally [i.p.]) or saline vehicle (VEH; 1 mL/kg; i.p.) beginning 24 h after surgery and once daily for 21 days (experiment 1). Motor (beam-balance/walk) and cognitive (Morris water maze [MWM]) assessments were conducted on post-operative Days 1-5 and 14-19, respectively. Cortical lesion volumes were quantified on Day 21. Sham controls were better versus all TBI groups. No differences in motor function or lesion volumes were observed among the TBI groups (p > 0.05). In contrast, GAL (2 mg/kg) enhanced MWM performance versus VEH and GAL (1 and 3 mg/kg; p < 0.05). In experiment 2, GAL (2 mg/kg) or VEH was combined with EE and the data were compared with the STD-housed groups from experiment 1. EE alone enhanced motor performance over the VEH-treated and GAL-treated (2 mg/kg) STD-housed groups (p < 0.05). Moreover, both EE groups (VEH or GAL) facilitated spatial learning and reduced lesion size versus STD + VEH controls (p < 0.05). No additional benefits were observed with the combination paradigm, which does not support the hypothesis. Overall, the data demonstrate that EE and once daily GAL (2 mg/kg) promote cognitive recovery after TBI. Importantly, the combined therapies did not negatively affect outcome and thus this therapeutic protocol may have clinical utility.

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The Effectiveness of Donepezil for Cognitive Rehabilitation After Traumatic Brain Injury

Cited by 42 publications

References 20 publications

Mild traumatic brain injury-induced hippocampal gene expressions: The identification of target cellular processes for drug development

Mild traumatic brain injury-induced hippocampal gene expressions: The identification of target cellular processes for drug development

Donepezil, an acetylcholine esterase inhibitor, and ABT-239, a histamine H3 receptor antagonist/inverse agonist, require the integrity of brain histamine system to exert biochemical and procognitive effects in the mouse

Galantamine and Environmental Enrichment Enhance Cognitive Recovery after Experimental Traumatic Brain Injury But Do Not Confer Additional Benefits When Combined

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