Neurogenic overactive bladder in spinal cord injury and multiple sclerosis: role of onabotulinumtoxinA.

People with neurogenic overactive bladder from either multiple sclerosis or spinal cord injury often suffer significant morbidity and decreased quality of life. Here we review the pathophysiology of neurogenic overactive bladder and the impact it can have on people with multiple sclerosis or spinal cord injury. We also address the various traditional treatment options and focus on the use of botulinum toxin A (specifically onabotulinumtoxinA) for this condition.

Exploring the role of nerve growth factor in multiple sclerosis: implications in myelin repair.

Multiple sclerosis (MS) is a chronic disease resulting from targeted destruction of central nervous system (CNS) myelin. MS is suggested to be an autoimmune disease involving the pathogenic activation of CD4(+) T cells by a foreign antigen in the peripheral blood. The activated CD4(+) T cells liberate inflammatory cytokines that facilitate the breakdown of the blood-brain barrier (BBB) promoting their passage into the CNS. Inside the CNS, CD4(+) T cells become re-activated by myelin proteins sharing a similar structure to the foreign antigen that initially triggered the immune response. The CD4(+) T cells continue to liberate inflammatory cytokines, such as tumor necrosis factor α (TNFα), which activates macrophages and antibodies responsible for the phagocytosis of myelin. Acute CNS lesions can be re-myelinated, however, the repair of chronic demyelinating lesions is limited, leading to permanent neurological deficits. Although current MS treatments reduce severity and slow disease progression, they do not directly repair damaged myelin. Henceforth, recent treatment strategies have focused on neurotrophins, such as nerve growth factor (NGF) for myelin repair. NGF promotes axonal regeneration, survival, protection and differentiation of oligodendrocytes (OGs) and facilitates migration and proliferation of oligodendrocyte precursors (OPs) to the sites of myelin damage. NGF also directly regulates key structural proteins that comprise myelin. Interestingly, NGF also induces the production of brain-derived neurotrophic factor (BDNF), another integral neurotrophin involved in myelination. The intricate signaling between neurotrophins and cytokines that governs myelin repair supports the role of NGF as a leading therapeutic candidate in white matter disorders, such as MS.

Neurogenesis in postnatal mouse dorsal root ganglia.

Neurogenesis continues in various regions of the central nervous system (CNS) throughout life. As the mitogen basic fibroblast growth factor (bFGF) can proliferate neuronal precursors of CNS neurons in culture, and is also upregulated within adult dorsal root ganglia following axotomy, it is possible that the postnatal dorsal root ganglia contain bFGF-responsive neuronal precursors. We undertook cell culture of postnatal mouse dorsal root ganglia to demonstrate neurogenesis. Basic FGF induced a cellular proliferative response in dorsal root ganglia cell culture. After 2 weeks in serum-free medium containing bFGF, neurons were rarely observed. However, following removal of bFGF and addition of trophic factors, many cells were observed that morphologically resembled dorsal root ganglia neurons, stained for neuronal markers, and generated action potentials. Furthermore, bromodeoxyuridine, used as a marker of cytogenesis, was detected in neurofilament-160(+) and/or microtubule-associated protein-2(+) cells that morphologically resembled neurons. In addition to bFGF, epidermal growth factor, nerve growth factor, and sonic hedgehog were also capable of generating spherical cell clusters that contained cells that stained for neuronal markers following the addition of trophic factors. These results suggest that early postnatal dorsal root ganglia contain neural precursors that appear to proliferate in response to various factors and can then be induced to differentiate into neurons. In conclusion, the existence of neural precursors and the possibility of neurogenesis in postnatal dorsal root ganglia may provide a greater range of plasticity available to somatosensory systems during growth or following injury, perhaps to replace ineffectual or dying neurons.