1. Designed, performed and analyzed experiments that characterized Erythropoietin binding sites in thalamus and cortex that were previously unknown. Further investigated the neuroprotective effects of Erythropoietin in mammal brain and identified novel crosstalk between two signaling pathways. These highly referenced publications significantly enhanced the research on neuroprotective potential of Erythropoietin by other scientists and biomedical companies
2. Digicaylioglu, M. et al. (1995) Localization of specific erythropoietin binding sites in defined areas of the mouse brain. PNAS, 92,3717-3720.
3. Marti, H. H. et al. (1996) Erythropoietin gene expression in human, monkey and murine brain. The

European journal of neuroscience, 8, 666-676.

1. Digicaylioglu, M. & Lipton, S. A. (2001) Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature, 412, 641-647.
2. Digicaylioglu, M., Kaul, M., Fletcher, L., Dowen, R. & Lipton, S. A. (2004) Erythropoietin protects cerebrocortical neurons from HIV-1/gp120-induced damage. Neuroreport,15, 761-763.
3. Discovered and described a novel synergy between two neuroprotectants, Erythropoietin and Insulin-like growth factor I. This novel combination provided acute and chronic neuroprotection in ischemic stroke and also significantly reduced the dosing of either drug.
   1. Digicaylioglu, M., Garden, G., Timberlake, S., Fletcher, L. & Lipton, S. A. (2004) Acute neuroprotective synergy of erythropoietin and insulin-like growth factor I. PNAS, 101, 9855-9860.
   2. Fletcher, L. et al. (2009) Intranasal delivery of erythropoietin plus insulin-like growth factor-I for acute neuroprotection in stroke. Laboratory investigation. J Neurosurgery, 111, 164-170.
   3. Kang, Y. J. et al. (2010) Erythropoietin plus insulin-like growth factor-I protects against neuronal damage in a murine model of human immunodeficiency virus-associated neurocognitive disorders. Annals of Neurology, 68, 342-352
4. Discovered and described a specific form of intranasal delivery, the transcribrosal administration, that further enhances the potential for acute neuroprotection. Investigated the transcribrosal uptake mechanisms and identified the rostral migratory stream as the main path into the brain. I designed a prototype of an applicator for this delivery method (Patent pending, UT HSC San Antonio).
   1. Fletcher, L. et al. (2009) Intranasal delivery of erythropoietin plus insulin-like growth factor-I for acute neuroprotection in stroke. Laboratory investigation. J Neurosurgery, 111, 164-170.
   2. Scranton, R. A., Fletcher, L., Sprague, S., Jimenez, D. F. & Digicaylioglu, M. (2011) The rostral migratory stream plays a key role in intranasal delivery of drugs into the CNS. PloS one, 6, e18711.
5. Identified and described micro RNA’s that are likely to play a role in neurodegeneration and neurorestoration after stroke and acute spinal cord injury. The identified microRNA’s include miR-29b, miR-21, miR-30b, miR- 107 and miR-137.
   1. Ziu, M., Fletcher, L., Rana, S., Jimenez, D. F. & Digicaylioglu, M. (2011) Temporal differences in microRNA expression patterns in astrocytes and neurons after ischemic injury. PloS one, 6, e14724.
   2. Ziu, M. et al. (2014) Spatial and temporal expression levels of specific microRNAs in a spinal cord injury mouse model and their relationship to the duration of compression. The spine journal, 14, 353-360.
6. Planned, conceived and executed the creation of a Shared Resource for Neurodegenerative Models at UT Health Science Center, San Antonio. The choice of animal models, the potential of the selected model for mimicking clinical presentation of a human disease and correct interpretation of the data are crucial for a productive and successful outcome of these experiments. Extensive training and appropriate setup of the surgical environment is essential to perform precise surgical procedures and exclude confounding factors. As a neurosurgeon I have generated protocols for surgical procedures and proper preoperative and postoperative care of models animal in accordance with IACUC rules. I have trained numerous technicians and NIH-funded scientists and provided over 5000 ischemic stroke, traumatic brain injury and spinal cord injury models to the scientific community. I have performed precise stereotaxic injections in selected brain areas of either drugs or cells and implanted devices into the CNS in over 1000 animals.
   1. Brochure describing the services provided by the Shared Resource for Neurodegenerative Models
   2. http://neurosurgery.uthscsa.edu/display.php?ps_id=55&pg=research.php (currently administered by Dr. Sayre)