zithromax and Brain-Injuries

Hypoxic-ischemic brain injury/encephalopathy affects about 1.15 million neonates per year, 96% of whom are born in low- and middle-income countries. Therapeutic hypothermia is not effective in this setting, possibly because injury occurs significantly before birth. Here, we studied the pharmacokinetics, safety, and efficacy of perinatal azithromycin administration in near-term lambs following global ischemic injury to support earlier treatment approaches.. Ewes and their lambs of both sexes (n=34, 141-143 days) were randomly assigned to receive azithromycin or placebo before delivery as well as postnatally. Lambs were subjected to severe global hypoxia-ischemia utilizing an acute umbilical cord occlusion model. Outcomes were assessed over a 6-day period.. While maternal azithromycin exhibited relatively low placental transfer, azithromycin-treated lambs recovered spontaneous circulation faster following the initiation of cardiopulmonary resuscitation and were extubated sooner. Additionally, peri- and postnatal azithromycin administration was well tolerated, demonstrating a 77-hour plasma elimination half-life, as well as significant accumulation in the brain and other tissues. Azithromycin administration resulted in a systemic immunomodulatory effect, demonstrated by reductions in proinflammatory IL-6 (interleukin-6) levels. Treated lambs exhibited a trend toward improved neurodevelopmental outcomes while histological analysis revealed that azithromycin supported white matter preservation and attenuated inflammation in the cingulate and parasagittal cortex.. Perinatal azithromycin administration enhances neonatal resuscitation, attenuates neuroinflammation, and supports limited improvement of select histological outcomes in an ovine model of hypoxic-ischemic brain injury/encephalopathy.

Topics: Animals; Azithromycin; Brain Injuries; Female; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Male; Neuroprotection; Placenta; Pregnancy; Resuscitation; Sheep

Systemic inflammation amplifies neonatal hypoxic-ischemic (HI) brain injury. Azithromycin (AZ), an antibiotic with anti-inflammatory properties, improves sensorimotor function and reduces tissue damage after neonatal rat HI brain injury. The objective of this study was to determine if AZ is neuroprotective in two neonatal rat models of inflammation-amplified HI brain injury.. Seven-day-old (P7) rats received injections of toll-like receptor agonists lipopolysaccharide (LPS) or Pam. In both LPS + HI and PAM + HI models, AZ improved sensorimotor function, survival, brain tissue preservation, and composite scores. Benefits increased with five- vs. three-dose AZ and declined with longer initiation delay.. Perinatal systemic infection is a common comorbidity of neonatal asphyxia brain injury and contributes to adverse outcomes. These data support further evaluation of AZ as a candidate treatment for neonatal neuroprotection.. AZ treatment decreases sensorimotor impairment and severity of brain injury, and improves survival, after inflammation-amplified HI brain injury, and this can be achieved even with a 2 h delay in initiation. This neuroprotective benefit is seen in models of inflammation priming by both Gram-negative and Gram-positive infections. This extends our previous findings that AZ treatment is neuroprotective after HI brain injury in neonatal rats.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Brain; Brain Injuries; Hypoxia-Ischemia, Brain; Inflammation; Lipopolysaccharides; Neuroprotective Agents; Oxygen; Rats; Rats, Wistar; Toll-Like Receptors