Lactate-Dehydrogenase-5 May Play a Key Role in the Disturbance of Brain Energy Caused by Tuberculous Meningitis

The conversion of pyruvate to lactate is primarily catalyzed by lactate-dehydrogenase-5 (LDH-5), which comprises four lactate-dehydrogenase-A (LDHA) subunits. However, the mechanism of LDH-5 in tuberculous meningitis (TBM) remains elusive.

Thirty-two samples of cerebrospinal fluid (CSF) were collected, including 15 from individuals without central nervous system (CNS) infectious diseases (control group) and 17 from individuals with TBM (TBM group). Based on the results of brain imaging, nine patients with TBM with meningeal enhancement were included in the meninges group. Eight patients with TBM with lesions in the brain parenchyma were included in the brain parenchyma group. The levels of adenosine triphosphatase (ATP), lactate, LDH-1, pyruvate and LDH-5 in the CSF were assessed. Subsequently, the levels of ATP, pyruvate and lactate, as well as the amplitude and frequency of action potentials (APs) in neurons overexpressing LDHA, were investigated.

Reduced levels of pyruvate and ATP and elevated levels of lactate and LDH-5 were observed in the CSF of individuals with TBM. The ATP level was decreased in the brain parenchyma group. In neurons with LDHA overexpression, the lactate level increased, while ATP and pyruvate levels, as well as the amplitude and frequency of APs, decreased.

Elevated levels of LDH-5 in the CNS of individuals with TBM may lead to a disturbance in brain energy and negatively affect neuronal activity.