Damage to neurons of the cerebral cortex in acute poisoning with baclofen and its combination with ethanol

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Abstract

BACKGROUND: The number of poisoning with a muscle relaxant baclofen has increased recently. The brain is one of the target organs in baclofen poisoning.

AIM: To identify and quantify cerebral cortex neuron damage in baclofen and baclofen ethanol poisoning.

MATERIAL AND METHODS: A histological study of rat cerebral cortex was performed. The controls (n = 5) received neither baclofen nor ethanol. Groups 1 and 3 received baclofen (85 mg/kg), whereas groups 2 and 4 received baclofen (85 mg/kg) and ethanol (7 ml/kg). Groups 1 and 3 were euthanized 4 h after the drug administration, whereas groups 2 and 4 were euthanized after 24 h. Histological sections were stained with hematoxylin and eosin and by the Nissl method and examined by light microscopy (×400). The number of damaged neurons was calculated. Statistical processing was performed by the nonparametric Mann–Whitney method.

RESULTS: Neurons with reversible and irreversible changes in the controls accounted for 13% and 9%, respectively. At 4 h after baclofen administration, neurons with reversible and irreversible changes accounted for 22% and 21%; 4 h after baclofen and ethanol administration, 24% and 29%; 24 h after baclofen administration, 25% and 37%, respectively. Baclofen and ethanol administration caused an increase in the share of neurons with reversible (27%) and irreversible (41%) changes. The differences between group 3 and the control group were significant, and the difference was significant when group 4 was compared with the control group and group 3.

CONCLUSION: Understanding the processes in the brain during baclofen and baclofen ethanol administration will allow the provision of medical care to this category of patients more effectively. The signs of brain neuron damage, along with the results of forensic chemical analysis, can be used to establish the immediate cause of death.

About the authors

Olga L. Romanova

Peoples’ Friendship University of Russia; Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology

Author for correspondence.
Email: olgpharm@yandex.ru
ORCID iD: 0000-0001-6356-9251
SPIN-code: 6727-9170

Cand. Sci. (Biol.)

Russian Federation, 8, Miklukho-Maklaya street, Moscow, 117198; Moscow

Arkady M. Golubev

Peoples’ Friendship University of Russia; Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology

Email: arkadygolubev@mail.ru
ORCID iD: 0000-0002-3165-0378
SPIN-code: 7890-2597

MD, Dr. Sci. (Med.)

Russian Federation, Moscow; Moscow

Alexey A. Churilov

Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology

Email: sandro-knaz-him@mail.ru
ORCID iD: 0000-0003-1018-8257
SPIN-code: 8648-0654
Russian Federation, Moscow

Dmitriy V. Sundukov

Peoples’ Friendship University of Russia

Email: sundukov_dv@rudn.university
ORCID iD: 0000-0001-8173-8944
SPIN-code: 2968-7961

MD, Dr. Sci. (Med.)

Russian Federation, Moscow

Maksim A. Kislov

The First Sechenov Moscow State Medical University (Sechenov University)

Email: smedik@gmail.com
ORCID iD: 0000-0002-9303-7640
SPIN-code: 3620-8930

MD, Dr. Sci. (Med.)

Russian Federation, Moscow

Anton V. Ershov

The First Sechenov Moscow State Medical University (Sechenov University)

Email: salavatprof@mail.ru
ORCID iD: 0000-0001-5758-8552
SPIN-code: 2059-3248

MD, Dr. Sci. (Med.)

Russian Federation, Moscow

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2. Fig. 1. Baclofen, 24 hours. The third layer of the cerebral cortex: tigrolysis of Nissl substance. Color according to Nissl, ×400.

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3. Fig. 2. Baclofen, 24 hours. The fourth layer of the cerebral cortex: decentralization of nuclei and nucleoli, shadow cells, severe changes. Hematoxylin-eosin staining, ×400.

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4. Fig. 3. Baclofen, 24 hours. The fifth layer of the cerebral cortex: dark neurons. Hematoxylin-eosin staining, ×400.

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5. Fig. 4. Baclofen + alcohol, 24 hours. The second layer of the cerebral cortex: prevailing of dark neurons. Hematoxylin-eosin staining, ×400.

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