Abstract
ObjectiveNeonatal meningitis caused by Escherichia coli results in significant mortality and neurological disabilities, with few effective treatments. Recently, we demonstrated that human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) transplantation attenuated E. coli-induced severe pneumonia, primarily by reducing inflammation and enhancing bacterial clearance. This study aimed to determine whether intraventricular transplantation of hUCB-MSCs attenuated the brain injury in E. coli meningitis in newborn rats.MethodsMeningitis without concomitant bacteremia was induced by intraventricular injection of 5 × 102 colony forming units of K1 (-) E. coli in rats at postnatal day (P)11, and hUCB-MSCs (1 × 105) were transplanted intraventricularly 6 h after induction of meningitis. Antibiotics was started 24 h after modeling.ResultMeningitis modeling induced robust proliferation of E. coli in the cerebrospinal fluid and increased mortality in rat pups, and MSC transplantation significantly reduced this bacterial growth and the mortality rate. Impaired sensorimotor function in the meningitis rats was ameliorated by MSCs injection. MSCs transplantation also attenuated meningitis caused brain injury including cerebral ventricular dilatation, brain cell death, reactive gliosis, and inflammatory response.ConclusionIntraventricular transplantation of hUCB-MSCs significantly improved survival and attenuated the brain injury via anti-inflammatory and antibacterial effects in experimental neonatal E. coli meningitis.
Highlights
Bacterial meningitis is the most common and fatal infection of the central nervous system (CNS) and is a major cause of morbidity and mortality worldwide.[1]
Survival and body weight To determine the beneficial effects of mesenchymal stem cells (MSCs) against meningitis, the survival rate and body weight gain in each group were monitored throughout the experiment
Bacterial counts To evaluate whether MSCs reduced the meningitis-induced bacterial burdens, colony forming units (CFU) were counted in the Cerebrospinal fluid (CSF) and blood from each study group at 6 h (P11), 24 h (P12), and 6 days (P17) after the induction of meningitis
Summary
Bacterial meningitis is the most common and fatal infection of the central nervous system (CNS) and is a major cause of morbidity and mortality worldwide.[1] Newborn infants are at higher risk because of their immature immunity and incomplete blood brain barrier (BBB). The mortality rate of neonatal bacterial meningitis varies according to the socio-economic status of the country, and ranges from 10 to 58%.2,3. The mortality rate has been reduced because of medical advances and the active use of antibiotic treatments, long-term neurological sequelae, which include hearing impairment, hydrocephalus, intracranial hemorrhage, mental retardation, and focal neurological deficit, have not changed and are still reported in almost 50% of survivors.[2] new therapeutic methods are urgently required to improve these adverse neurological complications induced by bacterial meningitis. Both bacterial pathogens and host inflammatory responses are known to be responsible for the pathophysiological mechanism of bacterial meningitis and the resultant brain injury and death.[4]
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