The continuous regeneration of glial cells arising from endogenous stem cell populations in the central nervous system (CNS) occurs throughout life in mammals. In the ongoing research to apply stem cell therapy to neurological diseases, the capacity to harness the multipotential ability of endogenous stem cell populations has become apparent. Such cell populations proliferate in response to a variety of injury states in the CNS, but in the absence of a supportive microenvironment they contribute little to any significant behavioral recovery. In the authors' laboratory and elsewhere, recent research on the regenerative potential of these stem cells in disease states such as spinal cord injury has demonstrated that the cells' proliferative potential may be greatly upregulated in response to appropriate growth signals and exogenously applied trophic factors. Further understanding of the potential of such multipotent cells and the mechanisms responsible for creating a favorable microenvironment for them may lead to additional therapeutic alternatives in the setting of neurological diseases. These therapies would require no exogenous stem cell sources and thus would avoid the ethical and moral considerations regarding their use. In this review the authors provide a brief overview of the enhancement of endogenous stem cell proliferation following neurological insult.
Nicholas C. Bambakidis, Nicholas Theodore, Peter Nakaji, Adrian Harvey, Volker K. H. Sonntag, Mark C. Preul and Robert H. Miller
Implications of his work for the understanding of cerebrovascular pathology and stroke
Sam Safavi-Abbasi, Cassius Reis, Melanie C. Talley, Nicholas Theodore, Peter Nakaji, Robert F. Spetzler and Mark C. Preul
✓ The history of apoplexy and descriptions of stroke symptoms date back to ancient times. It was not until the mid-nineteenth century, however, that the contributions of Rudolf Ludwig Karl Virchow, including his descriptions of the phenomena he called “embolism” and “thrombosis” as well as the origins of ischemia, changed the understanding of stroke. He suggested three main factors that conduce to venous thrombosis, which are now known as the Virchow triad. He also showed that portions of what he called a “thrombus” could detach and form an “embolus.” Thus, Virchow coined these terms to describe the pathogenesis of the disorder. It was also not until 1863 that Virchow recognized and differentiated almost all of the common types of intracranial malformations: telangiectatic venous malformations, arterial malformations, arteriovenous malformations, cystic angiomas (possibly what are now called hemangioblastomas), and transitional types of these lesions. This article is a review of the contributions of Rudolf Virchow to the current understanding of cerebrovascular pathology, and a summary of the life of this extraordinary personality in his many roles as physician, pathologist, anthropologist, ethnologist, and politician.
Sam Safavi-Abbasi, Noritaka Komune, Jacob B. Archer, Hai Sun, Nicholas Theodore, Jeffrey James, Andrew S. Little, Peter Nakaji, Michael E. Sughrue, Albert L. Rhoton and Robert F. Spetzler
The objective of this study was to describe the surgical anatomy and technical nuances of various vascularized tissue flaps.
The surgical anatomy of various tissue flaps and their vascular pedicles was studied in 5 colored silicone-injected anatomical specimens. Medical records were reviewed of 11 consecutive patients who underwent repair of extensive skull base defects with a combination of various vascularized flaps.
The supraorbital, supratrochlear, superficial temporal, greater auricular, and occipital arteries contribute to the vascular supply of the pericranium. The pericranial flap can be designed based on an axial blood supply. Laterally, various flaps are supplied by the deep or superficial temporal arteries. The nasoseptal flap is a vascular pedicled flap based on the nasoseptal artery. Patients with extensive skull base defects can undergo effective repair with dual flaps or triple flaps using these pedicled vascularized flaps.
Multiple pedicled flaps are available for reconstitution of the skull base. Knowledge of the surgical anatomy of these flaps is crucial for the skull base surgeon. These vascularized tissue flaps can be used effectively as single or combination flaps. Multilayered closure of cranial base defects with vascularized tissue can be used safely and may lead to excellent repair outcomes.
Nicholas C. Bambakidis, Eric M. Horn, Peter Nakaji, Nicholas Theodore, Elizabeth Bless, Tammy Dellovade, Chiyuan Ma, Xukui Wang, Mark C. Preul, Stephen W. Coons, Robert F. Spetzler and Volker K. H. Sonntag
Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration.
The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted.
Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means ± SDs, 46.9 ± 12.9 vs 20.9 ± 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups.
An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.