Michael P. Hefferan

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Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary(More)
Astrocytes in the CNS respond to tissue damage by becoming reactive. They migrate, undergo hypertrophy, and form a glial scar that inhibits axon regeneration. Therefore, limiting astrocytic responses represents a potential therapeutic strategy to improve functional recovery. It was recently shown that the epidermal growth factor (EGF) receptor is(More)
Tactile allodynia can be modeled in experimental animals by acutely blocking spinal glycine or GABA(A) receptors with intrathecal (i.t.) strychnine (STR) or bicuculline (BIC), respectively. To test the hypothesis that glycine and GABA effect cooperative (supra-additive) inhibition of touch-evoked responses in the spinal cord, male Sprague-Dawley rats,(More)
Transient spinal cord ischemia in humans can lead to the development of permanent paraplegia with prominent spasticity and rigidity. Histopathological analyses of spinal cords in animals with ischemic spastic paraplegia show a selective loss of small inhibitory interneurons in previously ischemic segments but with a continuing presence of ventral(More)
Transient spinal cord ischemia may lead to a progressive degeneration of spinal interneurons and subsequently to increased hind limb motor tone. In the present work we sought to characterize the rigidity and spasticity components of this altered motor function by: i) tonic electromyographic activity measured in gastrocnemius muscle before and after(More)
Amyotrophic lateral sclerosis (ALS) is characterized by loss of both upper and lower motor neurons. ALS progression is complex and likely due to cellular dysfunction at multiple levels, including mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress, axonal dysfunction, reactive astrocytosis, and mutant superoxide dismutase expression,(More)
BACKGROUND Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1) causes an inherited form of Amyotrophic Lateral Sclerosis (ALS). Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs) into the(More)
An important component for successful translation of cell replacement-based therapies into clinical practice is the utilization of large animal models to conduct efficacy and/or safety cell dosing studies. Over the past few decades, several large animal models (dog, cat, nonhuman primate) were developed and employed in cell replacement studies; however,(More)
In recent studies using a rat aortic balloon occlusion model, we have demonstrated that spinal grafting of rat or human neuronal precursors or human postmitotic hNT neurons leads to progressive amelioration of spasticity and rigidity and corresponding improvement in ambulatory function. In the present study, we characterized the optimal dosing regimen and(More)
Activation of p38 mitogen-activated protein kinase (MAPK) in the spinal cord has been implicated in the development and maintenance of pain states. In this study, we tested whether p38 MAPK is involved in the response to first-degree burn of the hind paw. This injury induces central sensitization leading to tactile allodynia and is mediated by activation of(More)