Amphetamine in recovery from brain injury

Hornstein, Andrew; Lennihan, Laura; Seliger, Glenn M.; Lichtman, Steven W.; Schroeder, Krista

doi:10.1080/026990596124647

Cited by 53 publications

(25 citation statements)

References 6 publications

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“…Several research groups have demonstrated similar long-lasting beneficial effects of amphetamine on functional recovery from brain injury in animals and Man (55)(56)(57), suggesting a common mechanism related to improvement in blood flow and facilitation of repair mechanisms.…”

Section: Discussionmentioning

confidence: 91%

Dynamic changes in N -methyl- d -aspartate receptors after closed head injury in mice: Implications for treatment of neurological and cognitive deficits

Biegon

Fry

Paden

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

219

164

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Traumatic brain injury is a leading cause of mortality and morbidity among young people. For the last couple of decades, it was believed that excess stimulation of brain receptors for the excitatory neurotransmitter glutamate was a major cause of delayed neuronal death after head injury, and several major clinical trials in severely head injured patients used blockers of the glutamate N-methyl-D-aspartate (NMDA) receptor. All of these trials failed to show efficacy. Using a mouse model of traumatic brain injury and quantitative autoradiography of the activity-dependent NMDA receptor antagonist MK801, we show that hyperactivation of glutamate NMDA receptors after injury is short-lived (<1 h) and is followed by a profound and long-lasting (>7 days) loss of function. Furthermore, stimulation of NMDA receptors by NMDA 24 and 48 h postinjury produced a significant attenuation of neurological deficits (blocked by coadministration of MK801) and restored cognitive performance 14 days postinjury. These results provide the underlying mechanism for the well known but heretofore unexplained short therapeutic window of glutamate antagonists after brain injury and support a pharmacological intervention with a relatively long (>24 h) time window easily attainable for treatment of human accidental head injury.H ead trauma is a leading cause of mortality and morbidity among young people in the western world (1). Traumatic and ischemic brain injury triggers a large, transient increase in excitatory amino acid transmitter efflux in the brain of experimental animals and human subjects (2-6). Glutamate activation of the N-methyl-D-aspartate (NMDA) receptor (NMDAR), which is a ligand-gated ion (calcium and sodium) channel, results in channel opening and ion influx into the cell. It has been suggested that this process mediates delayed excitotoxic neuronal death after brain ischemia and trauma (7,8), although the concept is not universally accepted (9, 10). Support for the involvement of NMDAR activation in neuronal death after brain injury has come from numerous studies showing that NMDAR antagonists reduce cell death and improve outcome in animal models of traumatic brain injury (TBI) and stroke. NMDAR antagonists appear to be most efficacious when given before or immediately after the insult and lose efficacy if administered Ͼ30-60 min postinjury (11)(12)(13)(14)(15).Microdialysis studies of extracellular glutamate in human TBI and stroke patients suggested that the increase in glutamate in humans is more sustained [6 h to several days (7, 8)] than in rodents, where it only lasts minutes (2-6). This result may have contributed to a decision to administer NMDAR antagonists in clinical trials of head injury for several days rather than once after severe nonpenetrating injury. All clinical trials of NMDAR antagonists to date failed to show efficacy. Furthermore, some of these trials had to be stopped prematurely because of increases in mortality and morbidity in the drug arm of the stroke trials (16-18), suggesting that prolonged bloc...

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Section: Discussionmentioning

confidence: 91%

Dynamic changes in N -methyl- d -aspartate receptors after closed head injury in mice: Implications for treatment of neurological and cognitive deficits

Biegon

Fry

Paden

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

219

164

View full text Add to dashboard Cite

show abstract

“…Performance on placebo became more variable over time, while cognitive efficiency and performance variability improved over time in the dextroamphetamine condition. A retrospective chart review of patients with severe TBI treated with 5 to 30 mg/d of dextroamphetamine for severe attentional or initiation problems found a positive effect on attention and participation at rehabilitation in 10 of 22 subjects [63]. No neuropsychological measures were conducted.…”

Section: Neurostimulantsmentioning

confidence: 99%

Pharmacological management of neurobehavioral disorders following traumatic brain injuryA state-of the-art review

Chew

Zafonte²

2009

JRRD

161

103

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Abstract-Pharmacological management of neurobehavioral disorders following traumatic brain injury (TBI) is common practice. However, the evidence available to guide this practice remains sparse. This review summarizes, in brief, the state of knowledge, organized via a time continuum from injury as well as by symptom complex. The areas of neuroprotection, hypoarousal, attention and memory deficits, aggression, agitation, depression, and mania are reviewed. The literature was searched with PubMed on the terms "traumatic brain injury" or "brain injury" with "pharmacology" (and the symptoms according to which this review is arranged). Additional searches were conducted with the specific symptoms as search terms, crossed with the therapeutic agents or drug classes discussed. Where a paucity of prospective data exists, case reports and retrospective studies are included. Studies to date have yielded minimal positive evidence for enhancing function, memory, and behavior after TBI. No single agent likely will become sentinel in the recovery process, and combination therapy in the acute and postacute settings are required. A need exists to further define the role of psychopharmacology in postacute TBI medicine and the specific characteristics of subpopulations who might benefit.

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“…The use of stimulants as, methylphenidate, has the most evidence to support their use in the treatment of sustained attention deficits, processing speed and more general cognitive functioning (Whyte et al, 1997(Whyte et al, , 2004. The psychostimulant, dextroamphetamine, may also have the added benefit of reducing the variability in performance in tasks of attention and working memory (Hornstein, Lennihan, Seliger, Lichtman, & Schroeder, 1996), but the studies at this time are limited. Cholinesterase inhibitors, initially developed in treating dementia, as donepezil and physostigmine, have been useful in treating the memory deficits and improving attention following TBI (Cardenas et al, 1994;Griffin et al, 2003;Taverni, Seliger, & Lichtman, 1998;Zhang et al, 2004).…”

Section: Pharmacological Treatment Of Cognitive and Neurobehavioral Imentioning

confidence: 99%

Call for an Integrative and Multi-Disciplinary Approach to Traumatic Brain Injury (TBI)

Mansour¹,

Lajiness-O’Neill²

2015

PSYCH

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Much has been gained in our understanding of the psychopathology, assessment, and treatment of TBI. Still lacking is the breadth and depth that an integrative and multi-disciplinary approach to TBI portends. While there is a greater awareness of a need for such a systems-based approach as evidenced by the number of professional organizations and government agencies recently advocating a need for standardization in the collection data in TBI, the application of multi-dimensional approach, and the development novel strategies to deliver prevention, assessment and treatment to large, diverse populations, we are still in the early stages in making this important shift. In the nearer term, there are clinical assessment and interventional programs that can be developed and empirically validated to bring us closer to this integrative, multi-disciplinary ideal. The following review calls for a universal diagnostic classification system for TBI, integration of pathophysiology and pharmacological and rehabilitative therapies, development of treatments addressing disorders comorbid with TBI, and the delivery of assessment and treatment services to large underserved populations.

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Amphetamine in recovery from brain injury

Abstract: A chart review of dextroamphetamine treatment in 27 traumatic brain injury patients during rehabilitation therapy suggests that amphetamine treatment enhanced the recovery and functional status of 15 patients.

Cited by 53 publications

References 6 publications

Dynamic changes in N -methyl- d -aspartate receptors after closed head injury in mice: Implications for treatment of neurological and cognitive deficits

Dynamic changes in N -methyl- d -aspartate receptors after closed head injury in mice: Implications for treatment of neurological and cognitive deficits

Pharmacological management of neurobehavioral disorders following traumatic brain injuryA state-of the-art review

Call for an Integrative and Multi-Disciplinary Approach to Traumatic Brain Injury (TBI)

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