A neurophysiological study on neurotoxicity of 2, 5-hexanedione: Auditory brainstem responses in rats

Abstract

Conduction disturbances in the central nervous system (CNS) of rats due to 2, 5-hexanedione (2, 5-HD) were examined, using auditory brainstem responses (ABRs). Ten male rats (Jcl-Wistar) were given subcutaneous injection of 2, 5-HD of 300 mg/kg/day five days a week for three weeks. For the control group, ten male rats (Jcl-Wistar) were employed. One week after the last administration, ABRs in rats were recorded at the scalp with subcutaneously inserted needle electrodes using the monopolar method under anesthesia. Intensity of the click sound stimulation was 25 dB and 60 dB over the threshold of human hearing level (25 dBHL and 60dBHL). Mixed nerve conduction velocity of the caudal nerve (MNCVca) and somatosensory cortical evoked potentials by electrical stimulation at the forepaw and medulla oblongata (SEP and SEP-M) were simultaneously recorded. The significant findings observed in rats administered 2,5-HD in comparison with the control rats were as follows: 1) Delayed latencies of 1st, IInd, IIIrd, IVth and Vth components of 60 dBHL sound ABR and 1st, IIIrd, IVth and Vth components of 25dBHL sound ABR; 2) Increased interpeak latencies (IPLs) between 1st and Vth components, IIIrd and Vth components, and IVth and Vth components of 25 dBHL sound ABR and between 1st and Vth components of 60 dBHL sound ABR; 3) Delayed latencies of PI and N1 components of SEP; and 4) Decreased MNCVca. Prolongation of IPL between IVth and Vth components of 25 dBHL sound ABR was considered to be conduction disturbance of auditory afferent pathway in CNS. The present results on SEP confirmed the previous finding that nerve conduction function in somatosensory afferent pathway was damaged by 2, 5-HD. The results of ABR indicate that measurement of ABR is a sensitive method to detect early disturbance of nerve conduction in CNS by neurotoxic substances which cause the dying back type axonopathy. © 1987, Japan Society for Occupational Health. All rights reserved.