Blood—spinal cord barrier

Banks WA, Kastin AJ, Arimura A (1998a) Effect of spinal cord injury on the permeability of the blood-brain and blood-spinal cord barriers to the neurotropin PACAP. Exp Neurol 151 116-123. 

Banks WA, Kastin AJ, Ehrensing CA (1994) Transport of blood-bome interleukin-la across the endothelial blood-spinal cord barrier of mice. J Physiol (London) 479 257-264. 

Juhler M, Barry DI, Offner H, Konat G, Klinken L, Paulson OB (1984) Blood-brain and blood-spinal cord barrier permeability during the course of experimental allergic encephalomyelitis in the rat. Brain Res 302 347-355. 

Pan W, Banks WA, Kastin AJ (1997b) Permeability of the blood-brain barrier and blood- spinal cord barriers to interferons. J Neu-roimmunol 76 105-111. 

Pan W, Zhang L, Liao J, Csernus B, Kastin AJ (2003b). Selective increase in TNF alpha permeation across the blood-spinal cord barrier after SCI. J Neuroimmunol 134 111-117. 

Blood—brain barrier/blood—spinal cord barrier... 

Rauch, M.F., Hynes, S.R., Bertram, J., Redmond, A., Robinson, R., Williams, C., Xu, H., Madri, J.A., Lavik, E.B., 2009. Engineering angiogenesis following spinal cord injury a coculture of neural progenitor and endothehal cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood-spinal cord barrier. Eur. J. Neurosci. 29 (1), 132-145. 

Garbuzova-Davis, S., Haller, E., Saporta, S., et al., 2007. Ultrastucture of blood-brain barrier and blood-spinal cord barrier in SODl mice modeling ALS. Brain Res. 1157, 126-137. 

Hemley SJ, Bilston LE, Cheng S et al (2012) Aquaporin-4 expression and blood-spinal cord barrier permeability in canalicular syringomyelia. J Neurosur Spine 17 602-612... 

Garbuzova-Davis S, Saporta S, Haller E et al (2007) Evidence of compromised blood -spinal cord barrier in early and late symptomatic SODl mice modeling ALS. PLoS One 2 el205... 

Bauer, H.C., A. Traweger, and H. Bauer. 2004. Proteins of the tight junction in the blood brain barrier. In Blood-spinal cord and brain barriers in health and disease, eds. H.S. Sharma and J. Westman, 1. San Diego Elsevier. 

Garbuzova-Davis S, Hernandez-Ontiveros DG, Rodrigues MC et al (2012) Impaired blood-brain barrier/spinal cord barrier in ALS patients. Brain Res 1469 114-128... 

Tso and Lam suggested that astaxanthin could be useful for prevention and treatment of neuronal damage associated with age-related macular degeneration and may also be effective in treating ischemic reperfusion injury, Alzheimer s disease, Parkinson s disease, spinal cord injuries, and other types of central nervous system injuries. Astaxanthin was found to easily cross the blood-brain barrier and did not form crystals in the eye. 

Another very important site for drug delivery is the central nervous system (CNS). The blood-brain barrier presents a formidable barrier to the effective delivery of most agents to the brain. Interesting work is now advancing in such areas as direct convective delivery of macromolecules (and presumably in the future macromolecular drug carriers) to the spinal cord [238] and even to peripheral nerves [239]. For the interested reader, the delivery of therapeutic molecules into the CNS has also been recently comprehensively reviewed... 

Intrathecal (IT) Into the subarachnoid space between two of the membranes (meninges) separating the spinal cord from the vertebral column. This route is used for drugs that do not penetrate the blood-brain barrier, but which are required for their central action (e.g., antibiotics). Drugs can also be injected spinally (into the epidural space) for local anaesthesia or analgesia. 

An important methodologic point about the majority of these studies is that they use a reduced preparation, in which the spinal cord is neurally isolated from the brain by a complete transection (129). The rationale for using this simplified preparation is that spinal reflex activity can be analyzed in the absence of supraspinal influences. However, transection may introduce other variables (i.e., ischemia, disruption of the blood-brain barrier, loss of tonic neural activity from supraspinal systems), which may result in drug effects on spinal reflexes that are quantitatively or even qualitatively different than those seen in the intact animal. Thus the following review of hallucinogen effects on spinal reflexes is organized into two main categories (a) studies in transected animals, and (b) those in decerebrate or intact preparations. 

In the central nervous system (brain and spinal cord), capillary endo-theUa lack pores and there is little transcytotic activity. In order to cross the blood-brain barrier, drugs must diffuse transcellularly, i.e., penetrate the luminal and basal membrane of endothelial cells. Drug movement along this path requires specific physicochemical properties (p. 26) or the presence of a transport mechanism (e.g., L-dopa, p. 188). Thus, the blood-brain barrier is permeable only to certain types of drugs. 

The aminopyridines (4-aminopyridine 3,4-diaminopyri-dine) accelerate spontaneous exocytosis at central and peripheral synapses. There is also an increase in the number of transmitter quanta released by a nerve action potential. This is probably the result of increased Ca++ inflow at the terminals due to a reduction of K+ conductance and prolongation of the nerve action potential. Muscle strength is increased in patients with the Lambert-Eaton myasthenic syndrome and in others poisoned with botuUnum E toxin (discussed later). Improvement in uncontrolled spasms, muscle tone, and pulmonary function is noted in patients with multiple sclerosis or long-standing spinal cord damage. Side effects that limit clinical utility include convulsions, restlessness, insomnia, and elevated blood pressure. Of the two agents, 3,4-diaminopyridine is the more potent and crosses the blood-brain barrier less readily. 

The blood-brain barrier foils most efforts to use the blood to measure the brain s chemistry, but researchers can get aroimd this obstacle by sampling cerebrospinal fluid (CSF). CSF is the fluid that circulates in the meninges of the brain and spinal cord and keeps the delicate tissues from getting rattled around and damaged in their hard, bony container. The brain makes CSF from blood, and certain metabolites get mixed in. One of these metabolites is 5-hydroxyindole acetaldehyde (5-FIIAA), a major metabolite of serotonin. Researchers who carefully puncture the meninges and extract a sample are rewarded with information concerning serotonin levels in the person s brain, as described below. 

Like spinal cord trauma, traumatic head injury consists of a primary injury, attributable to the mechanical insult itself, and a secondary injury, attributable to the series of systemic and local neurochemical changes that occur in brain after the initial traumatic insult (Klussmann and Martin-Villalba, 2005). The primary injury causes a rapid deformation of brain tissues, leading to rupture of neural cell membranes, release of intracellular contents, and disruption of blood flow and breakdown of the blood-brain barrier. In contrast, secondary injury to the brain tissue includes many neurochemical alterations such as release of cytokines, glial cell reactions involving both activated microglia and astroglia, and demyelination... 

Pan W., Kastin A. J., Bell R. L., and Olson R. D. (1999). Upregulation of tumor necrosis factor a transport across the blood-brain barrier after acute compressive spinal cord injury. J. Neurosci. 19 3649-3655. 

Frey, W.H. 2002. Bypassing the blood-brain barrier to deliver therapeutic agents to the brain and spinal cord. Drug Deliv Tech 2 46. 

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