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Poster 329: Ampakines Enhancement of Axonal Outgrowth by Cortical Neurons
PM&R
Poster 328 AIDS Associated Vacuolar Myelopathy - A Rehabilitation Challenge: A Case Report. Katherine D. Travnicek, MD (Johns Hopkins University, Baltimore, MD); Tapan Joshi; Sandeep Singh, MD. Disclosures: K. D. Travnicek, None. Patients or Programs: A 42-year-old black man presents with gait dysfunction Program Description: A 42-year-old black man with HIV/AIDS presents with a 2-year history of worsening ataxia, lower extremity weakness, and spasms. Neurological examination demonstrated muscle strength 3-4/5 in upper and lower extremities with absent proprioception, spasticity in bilateral hamstrings, positive Rhomberg and abnormal sensation in bilateral hands and feet. Bladder and bowel functions were normal. Setting: Inpatient rehabilitation facility. Results: Spinal MRI with contrast showed a high T2 signal intensity bilaterally in the posterior columns from C1 to T1 as well as in posterior lateral spinal cord extending from C2 to C5 in right side. Serum testing demonstrated CD4 count of 20, undetectable viral load, normal vitamin B12 level and non reactive RPR. Discussion: Recent advances in anti-retroviral therapy prolong life expectancy of HIV/AIDS patients, but they also make progressive neurologic complications such as AIDSassociated vacuolar myelopathy (VM) more common. Pathologically, VM is characterized by vacuolization in the posterior columns mimicking vitamin B12 deficiency. Occurring in advanced AIDS, VM causes spasticity, sensory impairment and muscle weakness but it mainly affects proprioception. Decreased proprioception impairs balance, spatial movement and ability to learn new skills. In severe cases, VM also involves the cervical spine affecting upper extremities as demonstrated in this patient. It is especially frustrating for a patient since he cannot ambulate or perform daily activities even after having functional strength. Currently, there is no evidence that anti-retroviral drugs can improve or slow VM progression. Conclusions: Although little is known about why AIDS VM occurs or how to treat it, it is important to recognize this disease. The comprehensive rehabilitation management of symptoms including compensatory strategies and adaptive equipment is a main stay of treatment for functional improvement and to promote independence. Keywords: Rehabilitation, HIV/AIDS, Proprioception, Vacuolar myelopathy.
Poster 329 Ampakines Enhancement of Axonal Outgrowth by Cortical Neurons. Vernon W. Lin, MD (Cleveland Clinic, Cleveland, OH); Christine M. Gall, PhD; Ching-Yi Lin. Disclosures: V. W. Lin, None.
Vol. 1, Iss. 9S, 2009
S247
Objective: The present studies tested if positive modulators of AMPA-type glutamate receptors (ampakines), which have been shown to increase neuronal BDNF expression in vitro and in vivo, also stimulate axonal growth by cortical neurons. Design: An in vitro test for the potential application of ampakine in the enhancement of axonal growth after trauma in the nervous system. Setting: Research laboratory in the Department of Anatomy & Neurobiology at the University of California, Irvine, CA. Participants: Rat E18 embryos. Interventions: Rat cortical neurons were cultured onto a poly-L-lysine coated glass substrate in the ‘somal well of a Microfluidic Culture Platform (MCP) (Park et al. Nat. Protoc. 1:2128-36, 2006), which includes fluidic-isolation compartments (i.e., somal and axonal wells) separated by a grooved bridge region into which neurites can grow. Ampakines were applied to the MCP somal well, the axonal well, or both, and the length of neurite elongation into the bridge region was evaluated after 1-4 days of ampakine exposure. Main Outcome Measures: The length of neurite elongation into the bridge region of MCP was evaluated after 1-4 days of ampakine exposure with or without antagonist. Results: Treatments with the ampakines CX614 and CX929 significantly increased neurite outgrowth. These effects were not site- (soma vs axon) specific and were comparable across doses tested (0.1 - 10 M for CX614 and 0.5 to 50 M for CX929). While increases in mature BDNF protein were associated with ampakine treatment of dissociated cortical neurons, the growth promoting effects of ampakine treatment were not blocked by addition of the BDNF scavenger, TrkB-Fc. However, the Trk signaling antagonist K252a attenuated ampakine effects on neurite length most reliably after application to the somal well. Conclusions: These results demonstrate that ampakines enhance axonal growth and suggest that the growth response is mediated, at least in part, by increases in the signaling of multiple neurotrophins (e.g., BDNF and NGF). These results further support the possibility that ampakines might be used to facilitate reactive axonal growth following CNS damage. Keywords: Rehabilitation, BDNF, Axonal growth, Microfluidic culture platform.
Poster 330 An Elusive and Overlooked Etiology of Spinal Cord Injury: The Human T Cell Lymphotropic Virus: A Case Report. Hector A. Miranda, MD (Jackson Memorial Hospital, Miami, FL); Gregory Samson, MD. Disclosures: H. A. Miranda, Jackson Memorial Hospital, Employment. Patients or Programs: A 60-year-old African American man. Program Description: A 60-year-old African American man with nicotine and alcohol dependence, and past history of diabetes mellitus type II who referred a 6-month history of
Poster 328 AIDS Associated Vacuolar Myelopathy - A Rehabilitation Challenge: A Case Report. Katherine D. Travnicek, MD (Johns Hopkins University, Baltimore, MD); Tapan Joshi; Sandeep Singh, MD. Disclosures: K. D. Travnicek, None. Patients or Programs: A 42-year-old black man presents with gait dysfunction Program Description: A 42-year-old black man with HIV/AIDS presents with a 2-year history of worsening ataxia, lower extremity weakness, and spasms. Neurological examination demonstrated muscle strength 3-4/5 in upper and lower extremities with absent proprioception, spasticity in bilateral hamstrings, positive Rhomberg and abnormal sensation in bilateral hands and feet. Bladder and bowel functions were normal. Setting: Inpatient rehabilitation facility. Results: Spinal MRI with contrast showed a high T2 signal intensity bilaterally in the posterior columns from C1 to T1 as well as in posterior lateral spinal cord extending from C2 to C5 in right side. Serum testing demonstrated CD4 count of 20, undetectable viral load, normal vitamin B12 level and non reactive RPR. Discussion: Recent advances in anti-retroviral therapy prolong life expectancy of HIV/AIDS patients, but they also make progressive neurologic complications such as AIDSassociated vacuolar myelopathy (VM) more common. Pathologically, VM is characterized by vacuolization in the posterior columns mimicking vitamin B12 deficiency. Occurring in advanced AIDS, VM causes spasticity, sensory impairment and muscle weakness but it mainly affects proprioception. Decreased proprioception impairs balance, spatial movement and ability to learn new skills. In severe cases, VM also involves the cervical spine affecting upper extremities as demonstrated in this patient. It is especially frustrating for a patient since he cannot ambulate or perform daily activities even after having functional strength. Currently, there is no evidence that anti-retroviral drugs can improve or slow VM progression. Conclusions: Although little is known about why AIDS VM occurs or how to treat it, it is important to recognize this disease. The comprehensive rehabilitation management of symptoms including compensatory strategies and adaptive equipment is a main stay of treatment for functional improvement and to promote independence. Keywords: Rehabilitation, HIV/AIDS, Proprioception, Vacuolar myelopathy.
Poster 329 Ampakines Enhancement of Axonal Outgrowth by Cortical Neurons. Vernon W. Lin, MD (Cleveland Clinic, Cleveland, OH); Christine M. Gall, PhD; Ching-Yi Lin. Disclosures: V. W. Lin, None.
Vol. 1, Iss. 9S, 2009
S247
Objective: The present studies tested if positive modulators of AMPA-type glutamate receptors (ampakines), which have been shown to increase neuronal BDNF expression in vitro and in vivo, also stimulate axonal growth by cortical neurons. Design: An in vitro test for the potential application of ampakine in the enhancement of axonal growth after trauma in the nervous system. Setting: Research laboratory in the Department of Anatomy & Neurobiology at the University of California, Irvine, CA. Participants: Rat E18 embryos. Interventions: Rat cortical neurons were cultured onto a poly-L-lysine coated glass substrate in the ‘somal well of a Microfluidic Culture Platform (MCP) (Park et al. Nat. Protoc. 1:2128-36, 2006), which includes fluidic-isolation compartments (i.e., somal and axonal wells) separated by a grooved bridge region into which neurites can grow. Ampakines were applied to the MCP somal well, the axonal well, or both, and the length of neurite elongation into the bridge region was evaluated after 1-4 days of ampakine exposure. Main Outcome Measures: The length of neurite elongation into the bridge region of MCP was evaluated after 1-4 days of ampakine exposure with or without antagonist. Results: Treatments with the ampakines CX614 and CX929 significantly increased neurite outgrowth. These effects were not site- (soma vs axon) specific and were comparable across doses tested (0.1 - 10 M for CX614 and 0.5 to 50 M for CX929). While increases in mature BDNF protein were associated with ampakine treatment of dissociated cortical neurons, the growth promoting effects of ampakine treatment were not blocked by addition of the BDNF scavenger, TrkB-Fc. However, the Trk signaling antagonist K252a attenuated ampakine effects on neurite length most reliably after application to the somal well. Conclusions: These results demonstrate that ampakines enhance axonal growth and suggest that the growth response is mediated, at least in part, by increases in the signaling of multiple neurotrophins (e.g., BDNF and NGF). These results further support the possibility that ampakines might be used to facilitate reactive axonal growth following CNS damage. Keywords: Rehabilitation, BDNF, Axonal growth, Microfluidic culture platform.
Poster 330 An Elusive and Overlooked Etiology of Spinal Cord Injury: The Human T Cell Lymphotropic Virus: A Case Report. Hector A. Miranda, MD (Jackson Memorial Hospital, Miami, FL); Gregory Samson, MD. Disclosures: H. A. Miranda, Jackson Memorial Hospital, Employment. Patients or Programs: A 60-year-old African American man. Program Description: A 60-year-old African American man with nicotine and alcohol dependence, and past history of diabetes mellitus type II who referred a 6-month history of