1.
Neurogenic inflammation and its role in migraine.
Ramachandran, R
Seminars in immunopathology. 2018;(3):301-314
Abstract
The etiology of migraine pain involves sensitized meningeal afferents that densely innervate the dural vasculature. These afferents, with their cell bodies located in the trigeminal ganglion, project to the nucleus caudalis, which in turn transmits signals to higher brain centers. Factors such as chronic stress, diet, hormonal fluctuations, or events like cortical spreading depression can generate a state of "sterile inflammation" in the intracranial meninges resulting in the sensitization and activation of trigeminal meningeal nociceptors. This sterile inflammatory phenotype also referred to as neurogenic inflammation is characterized by the release of neuropeptides (such as substance P, calcitonin gene related peptide) from the trigeminal innervation. This release leads to vasodilation, plasma extravasation secondary to capillary leakage, edema, and mast cell degranulation. Although neurogenic inflammation has been observed and extensively studied in peripheral tissues, its role has been primarily investigated in the genesis and maintenance of migraine pain. While some aspects of neurogenic inflammation has been disregarded in the occurrence of migraine pain, targeted analysis of factors have opened up the possibilities of a dialogue between the neurons and immune cells in driving such a sterile neuroinflammatory state in migraine pathophysiology.
2.
A speculative essay on retinoic acid regulation of neural stem cells in the developing and aging olfactory system.
Rawson, NE, LaMantia, AS
Experimental gerontology. 2007;(1-2):46-53
Abstract
Circulating signals like the acidic derivative of vitamin A: retinoic acid (RA) may regulate resident stem cells in the adult nervous system, particularly in the olfactory pathway. RA is an essential factor for inducing neural stem or precursor cells that give rise to olfactory receptor neurons (ORNs) and olfactory bulb (OB) interneurons (OBINs) during embryonic development. Similar precursors in the adult brain constantly generate new ORNs and OBINs, and embryonic signaling pathways, like that via RA, may be retained or reactivated for this purpose. We have shown that RA regulates neural precursors in the embryonic and adult olfactory pathway. Moreover, RA administration after olfactory system damage stimulates an immune response and yields a more rapid recovery of olfactory-guided behavior. We suggest that olfactory integrity may be maintained by RA-mediated regulation of neurogenesis as well as local immune responses, and that aging compromises these mechanisms. The chemical senses, particularly olfaction, decline in aged individuals, and RA (via vitamin A) levels may also decline, perhaps due to changes in appetite and food intake. This synergy may result in a high prevalence of olfactory pathology in aged individuals.
3.
Autoantibodies in paraneoplastic neurological syndrome.
Inuzuka, T
The American journal of the medical sciences. 2000;(4):217-26
Abstract
Paraneoplastic neurological syndrome is a rare disorder caused by the secondary effects of cancer and is thought to be immune-mediated. A high titer of autoantibodies in the patient's serum and cerebrospinal fluid, directed against both neurons and tumor, have been detected in some forms of this syndrome. These autoantibodies are considered the result of an immunological response to tumor and may cross-react with cells of the nervous system, causing neuronal damage. Specific forms of this syndrome are often associated with specific antineuronal antibodies and tumors. The onset of neurological symptoms and detection of these antibodies often precede the diagnosis of the tumor; therefore, detection of these antibodies greatly assists the diagnosis of this syndrome and prompts investigations for the underlying tumor. The pathogenicity of these antineuronal antibodies has been proven in only a few cases, such as that of anti-voltage gated calcium-channel antibodies in Lambert-Eaton myasthenic syndrome. The selective involvement of specific types of neurons has not been fully elucidated. The target spectrum of some of these antineuronal antibodies correlates well with the neurological symptoms, but that of others is wider than expected from the symptoms. Interesting evidence has suggested that these antionconeuronal antibodies can suppress tumor growth. The discovery of new antibodies and characterization of target molecules have been reported with advances in the field of molecular biology. A more detailed understanding of the relationship between the cancer and the neural involvement from the molecular biological standpoint may lead to rational tumor therapy and elucidation of the mechanism of neuronal death. Here, major clinical forms with well-known antineuronal antibodies and specific tumors are reviewed; for each antineuronal antibody, the target antigens and its putative role in the pathogenesis of this syndrome are described.