Inosine enhances recovery of grasp following cortical injury to the primary motor cortex of the rhesus monkey

Moore, Tara; Pessina, Monica A.; Finklestein, Seth P.; Killiany, Ronald; Bowley, Bethany; Benowitz, Larry I.; Rosene, Douglas L.

doi:10.3233/rnn-160661

Cited by 15 publications

(15 citation statements)

References 118 publications

(174 reference statements)

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“…Consistent with these results, previous studies have reported the involvement of cerebral cortex lesions in the functional recovery of manual dexterity [ 27 ]. The impaired movement of the affected hand and the relative increase in reaction time in stroke patients have been reported to be correlated with the size of the brain lesions in the ipsilateral hemisphere [ 43 , 44 ].…”

Section: Discussionsupporting

confidence: 89%

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Assessment of Hand Motor Function in a Non-human Primate Model of Ischemic Stroke

Won

Choi

et al. 2020

Exp Neurobiol

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Ischemic stroke results from arterial occlusion and can cause irreversible brain injury. A non-human primate (NHP) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. We evaluated hand motor function in a cynomolgus monkey model of ischemic stroke. Endovascular transient middle cerebral artery occlusion (MCAO) with an angiographic microcatheter induced cerebral infarction. In vivo magnetic resonance imaging mapped and measured the ischemia-induced infarct lesion. In vivo diffusion tensor imaging (DTI) of the stroke lesion to assess the neuroplastic changes and fiber tractography demonstrated three-dimensional patterns in the corticospinal tract 12 weeks after MCAO. The hand dexterity task (HDT) was used to evaluate fine motor movement of upper extremity digits. The HDT was modified for a home cage-based training system, instead of conventional chair restraint training. The lesion was localized in the middle cerebral artery territory, including the sensorimotor cortex. Maximum infarct volume was exhibited over the first week after MCAO, which progressively inhibited ischemic core expansion, manifested by enhanced functional recovery of the affected hand over 12 weeks after MCAO. The total performance time decreased with increasing success rate for both hands on the HDT. Compensatory strategies and retrieval failure improved in the chronic phase after stroke. Our findings demonstrate the recovery of fine motor skill after stroke, and outline the behavioral characteristics and features of functional disorder of NHP stroke model, providing a basis for assessing hand motor function after stroke.

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Section: Discussionsupporting

confidence: 89%

“…The HDT was used to evaluate fine motor functions of the hand and digits, as described in previous rhesus monkey studies by Moore et al [ 27 ]. The HDT used in this study was slightly modified, whereby the testing apparatus was designed for a cage-based training system.…”

Section: Methodsmentioning

confidence: 99%

Assessment of Hand Motor Function in a Non-human Primate Model of Ischemic Stroke

Won

Choi

et al. 2020

Exp Neurobiol

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“…Under physiologic conditions, blood levels of inosine are increased by exercise and ingestion of certain foods (organ meats, beer, spinach) and exhibit diurnal variations. Over the past two decades, inosine has been shown to evoke significant improvements in motor function and visceral organ control in preclinical models of neurologic injury including SCI [19][20][21][22][23][24], stroke [25][26][27][28][29], traumatic brain injury [30], multiple sclerosis (MS) [31][32][33][34][35] and Parkinson's disease (PD) [36] through its ability to enhance the growth of axon collaterals from undamaged neurons. The basis of these beneficial effects stems from its antioxidant, anti-inflammatory, axogenic and neuroprotective properties (reviewed in [37]).…”

Section: Inosinementioning

confidence: 99%

Inosine – a Multifunctional Treatment for Complications of Neurologic Injury

Doyle¹,

Cristofaro²,

Sullivan³

et al. 2018

Cell Physiol Biochem

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Spinal cord injury (SCI) caused by trauma or disease leads to motor and sensory abnormalities that depend on the level, severity and duration of the lesion. The most obvious consequence of SCI is paralysis affecting lower and upper limbs. SCI also leads to loss of bladder and bowel control, both of which have a deleterious, life-long impact on the social, psychological, functional, medical and economic well being of affected individuals. Currently, there is neither a cure for SCI nor is there adequate management of its consequences. Although medications provide symptomatic relief for the complications of SCI including muscle spasms, lower urinary tract dysfunction and hyperreflexic bowel, strategies for repair of spinal injuries and recovery of normal limb and organ function are still to be realized. In this review, we discuss experimental evidence supporting the use of the naturally occurring purine nucleoside inosine to improve the devastating sequelae of SCI. Evidence suggests inosine is a safe, novel agent with multifunctional properties that is effective in treating complications of SCI and other neuropathies.

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“…The basis for this difference is likely in part a difference in the underlying biology between rodents and humans and suggests that the response to injury in the rodent may be different than that in the primate. Our NHP model of cortical injury is a well-controlled and minimally variable model that has been tested and validated in our laboratory and used to assess various therapeutic agents (Moore et al 2012;Moore et al 2013;Moore et al 2016). Results have consistently found that focal injury to the hand representation of motor cortex produces a well-characterized deficit in fine motor function, which is very similar to that seen in human stroke patients.…”

Section: Comparison With Similar Scalementioning

confidence: 85%

A method for assessing recovery of fine motor function of the hand in a rhesus monkey model of cortical injury: an adaptation of the Fugl–Meyer Scale and Eshkol–Wachman Movement Notation

Pessina

Bowley

Rosene

et al. 2019

Somatosensory & Motor Research

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Motor dysfunction of the upper extremity can result from stroke, cortical injury and neurological diseases and causes significant disruption of activities of daily living. While some spontaneous recovery in terms of compensatory movements does occur after injury to cortical motor areas, full recovery is rare. The distinction between complete recovery and compensatory recovery is important as the development of compensatory movements in the upper extremity may not translate into full functional use in human patients. However, current animal models of stroke do not distinguish full recovery from compensatory recovery. We have developed a Non-Human Primate Grasp Assessment Scale (GRAS) to quantify the precise recovery of composite movement, individual digit action, and finger-thumb pinch in our rhesus monkey model of cortical injury. To date, we have applied this GRAS scale to assess the recovery of fine motor function of the hand in young control and cell-therapy treated monkeys with cortical injury confined to the hand representation in the dominant primary motor cortex. We have demonstrated that with this scale we can detect and quantify significant impairments in fine motor function of the hand, the development of compensatory function during recovery and finally a return to full fine motor function of the hand in monkeys treated with a cell therapy.

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Inosine enhances recovery of grasp following cortical injury to the primary motor cortex of the rhesus monkey

Abstract: These findings demonstrate that inosine can enhance recovery of function following cortical injury in monkeys.

Cited by 15 publications

References 118 publications

Assessment of Hand Motor Function in a Non-human Primate Model of Ischemic Stroke

Assessment of Hand Motor Function in a Non-human Primate Model of Ischemic Stroke

Inosine – a Multifunctional Treatment for Complications of Neurologic Injury

A method for assessing recovery of fine motor function of the hand in a rhesus monkey model of cortical injury: an adaptation of the Fugl–Meyer Scale and Eshkol–Wachman Movement Notation

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