GET THE APP

Targeting toll-like receptors to reduce brain injury
..

Neurological Disorders

ISSN: 2329-6895

Open Access

Targeting toll-like receptors to reduce brain injury


International Congress on Neuroimmunology and Therapeutics

DoubleTree by Hilton Hotel San Francisco Airport, San Francisco, CA, USA

Carina Mallard

Posters-Accepted Abstracts: J Neurol Disord

Abstract :

Toll-like receptors (TLRs), a family of innate immune receptors, play a critical role in mediating inflammation in response to both pathogens and non-pathogen stimuli, so called sterile inflammation, such as cerebral hypoxia-ischemia. We have studied the contribution of TLRs to injury in the developing brain and showed that TLRs are regulated in the newborn brain following both systemic inflammation and after neonatal cerebral hypoxia-ischemia. LPSa TLR-4 agonist, given to fetal sheep at midgestation, results in brain injury similar to that observed in preterm infants. Chronic systemic exposure of either LPS or a TLR-1/2 agonist (Pam3CSK4) during the early neonatal period impairs both grey and white matter development in mice and genetic inhibition of TLR-2 protects against neonatal hypoxia-ischemia. Stimulation of TLRs can also increase the vulnerability to subsequent insults and thereby exaggerate brain injury in the neonate. We showed that stimulation of TLR-3 or TLR-4 renders newborn rodents highly susceptible to hypoxia-ischemia and that the increased vulnerability is dependent on the TLR adaptor proteins MyD88 and TRIF. In a recent study we have further explored the neuroprotective potential of a novel class of immunomodulation peptides following LPS-induced brain injury. In summary, there is convincing data to show that inflammatory mechanisms contribute to perinatal brain injury. TLRs seem to play an important role in mediating these neurotoxic effects on the developing brain.

Google Scholar citation report
Citations: 1343

Neurological Disorders received 1343 citations as per Google Scholar report

Neurological Disorders peer review process verified at publons

Indexed In

 
arrow_upward arrow_upward