D-Lactic acid-induced neurotoxicity in a calf model

Area of Science:

• Veterinary Neurology
• Gastroenterology
• Biochemistry

Background:

• Lactic acidosis (LA) is a complication of short-bowel syndrome and other gastrointestinal disorders.
• LA is associated with central nervous system (CNS) dysfunction, including ataxia and coma.
• The specific cause of neurological impairment in LA remains unclear.

Purpose of the Study:

• To investigate whether nervous tissue acidification or d-lactic acid is responsible for decreased neurological function.
• To differentiate the neurotoxic effects of d-lactate from general acidosis.

Main Methods:

• Eight Holstein calves were surgically fitted with intravenous and cerebrospinal fluid (CSF) catheters.
• Calves were infused with either dl-lactic acid (dl-LA), l-lactic acid (l-LA), hydrochloric acid (HCl), or saline for 6 hours.
• Neurological function was assessed, and blood/CSF acid-base parameters were monitored.

Main Results:

• dl-LA infusion induced ataxia and significantly impaired CNS function compared to other treatments.
• HCl infusion caused severe acidemia and CSF acidosis but minimal neurological effects.
• dl-LA induced less severe acidemia than HCl but greater neurological impairment, suggesting d-lactate's direct neurotoxicity.

Conclusions:

• D-lactate, not systemic acidosis, is directly responsible for the neurological dysfunction observed in lactic acidosis.
• L-lactic acid has minimal impact on neurological function.
• These findings are crucial for understanding and managing gastrointestinal disorders causing lactic acidosis.