Martin Marsala, M.D.

Aortic occlusion will induce paralysis. Using a well-developed model of thoracic aortic occlusion with a 2 F Fogarty catheter passed from the femoral artery of the rat, we have shown that the mechanism of such ischemic deficit is primarily the result of a selective degeneration of small inhibitory GABA-ergic and glycinergic neurons localized in lumbosacral segments. Using a technique of selective spinal cord cooling we have also shown that a moderate intraischemic or early postischemic spinal hypothermia can provide a significant protection. However, once a significant population of spinal neurons is lost the corresponding neurological deficit is irreversible. Recently, using isolated spinal neuronal precursors or human hNT cells we have shown a long-term survival and rapid maturation of grafted cells at 2-3 months after transplantation if implanted into previously ischemic spinal cord segments. Majority of grafted cells developed inhibitory neurotransmitter phenotype (GABA) as confirmed by confocal microscopy. Significant improvement of neurological function and improvement in motor evoked potentials was also seen. Further studies will employ several other cell lines including human neural precursors or pluripotent stem cell lines and analyzed for their therapeutic potential when grafted spinally in animals with ischemia-induced paraplegia. The goal will be to identify differentiation potential, long term survival and functionality of grafted cells. In addition, electronoptical analysis will be used to identify the development of synapses between grafted cells and persisting host neurons.

Selected Publications 
Hefferan ML, Kucharova K, Kinjo K, Kakinohana O, Sekerkova G, Nakamura S, Fuchigami T, Tomori Z, Yaksh TL, Kurtz N, Marsala M. Spinal astrocyte glutamate receptor 1 overexpression after ischemic insult facilitates behavioral signs of spasticity and rigidity. J Neurosci. 27:11179-11191, 2007.

Hedlund E, Hefferan MP, Marsala M, Isacson O. Cell therapy and stem cells in animal models of motorneuron disorders. Eur J Neurosci. 26:1721-1737., 2007.

Cizkova D, Kakinohana O, Kucharova K, Marsala S, Johe K, Hazel T, Hefferan MP, Marsala M. Functional recovery in rats with ischemic paraplegia after spinal grafting of human spinal stem cells. Neurosci. 147:546-560, 2007.

Kucharova K, Lukacova N, Pavel J, Radonak J, Hefferan MP, Kolesar D, Kolessaova M, Marsala M, Marsala J. Spatiotemporal alterations of the NO/NOS neuronal pools following transient abdominal aorta occlusion: morphological and biochemical studies in the rabbit Cell Mol Neurobiol. 26:1295-1310, 2006.

 Marsala M, Kakinohana O, Hefferan MP, Cizkova D, Kinjoh K, Marsala S. Synaptogenesis and amino acid release from long term embryonic rat spinal cord neuronal culture using tissue culture inserts.J Neurosci Methods. 141:21-7, 2005

Marsala M, Kakinohana O, Yaksh TL, Tomori Z, Marsala S, Cizkova D.  Spinal implantation of hNT neurons and neuronal precursors: graft survival and functional effects in rats with ischemic spastic paraplegia. Eur J Neurosci;20:2401-14, 2004

Kakinohana O, Cizkova D, Tomori Z, Hedlund E, Marsala S, Isacson O, Marsala M.  Region-specific cell grafting into cervical and lumbar spinal cord in rat: a qualitative and quantitative stereological study. Exp Neurol. 190:122-32, 2004

Marsala J, Lukacova N, Cizkova D, Lukac I, Kucharova K, Marsala M. Premotor nitric oxide synthase immunoreactive pathway connecting lumbar segments with the ventral motor nucleus of the cervical enlargement in the dog. J Chem Neuroanat. 27:43-54. 2004