Acute stroke, spinal cord injury, and neuropathy
A single intravenous (i.v.) dose of TUDCA administered to rats 60 min after occlusion of the middle cerebral artery markedly reduced infarct size and apoptosis and preserved mitochondrial integrity (Rodrigues et al., 2002). The single i.v. dose resulted in a significant increase in brain UDCA levels from near undetectable levels to 0.15 nmol/g. TUDCA was also found to have an anti-inflammatory effect in the context of the central nervous system. TUDCA reduced glial cell activation and microglial chemotaxis and reduced expression of the MCP-1 chemoattractant and vascular adhesion proteins such as VCAM-1 in microglial cells and astrocytes treated with either interferon gamma (IFN-γ) or lipopolysaccharide and IFN-γ (Yanguas-Casás et al., 2014). Injection of TUDCA into the carotid artery 1 h prior to or up to 6 h after collagenase injection into the striatum to induce hemorrhagic lesions decreased lesion volumes, peri-hematoma apoptosis, and caspase activity at 2 days by about 50%, as well as decreased NF-κB and increased AKT activation that was associated with neurobehavioral improvement (Rodrigues et al., 2003). TUDCA injected intraperitoneally 1 min after spinal cord crush injury decreased apoptosis and corresponding tissue injury (Colak et al., 2008). In a phase II open-label study of oral doxycycline and TUDCA taken three times/day for 1 year in patients with transthyretin amyloidosis (ATTR), progression of neuropathy was stabilized (Obici et al., 2012).