EFFECT OF CHLORAL HYDRATE ON MORPHOLOGICAL CHANGES IN THE NEOCORTEX AND FUNCTIONAL STATE OF OLD MALE RATS

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In order to avoid obtaining distorted results at the stage of preclinical study of new pharmaceutical substances and therapeutic strategies, it is necessary to take into account the features and possible influence of the age of the animal and the anesthesia used on the outcome of the experiment. We studied the effect of chloral hydrate on morphological changes in neurons and the reaction of neocortical microglia and the functional state of old male Wistar rats (24 months). Differences were assessed in control rats and in the group using chloral hydrate at the dose required to achieve anesthesia (400 mg/kg animal weight) after 48 hours. After the application of chloral hydrate, the surviving animals (mortality rate 37.5%) showed a significant increase in the signs of neurological deficit in the form of motor, sensory and behavioral disorders compared to the rats of the control group. In the fronto-parietal region of the neocortex of the surviving animals, the expression level of the Iba-1 protein was significantly higher than in the control, neurons and microgliocytes with pronounced morphological changes were noted, while their number did not significantly differ from that in the control group. The obtained results suggest that the adverse effect in the early period after anesthesia with chloral hydrate without model surgical intervention in old rats, which manifests itself in the form of a deterioration in the functional state and mortality, can be realized due to the activation of microglia in the fronto-parietal region of the neocortex. However, the process of determining the specific structure of the brain, the activation of microglia in which is more responsible for the formation of neurological disorders, is quite complex and needs further study. In fundamental and preclinical studies of neuroprotective effects, in which old rats are used as the object of study and chloral hydrate is used as an anesthetic, these features must be taken into account.

作者简介

N. Shcherbak

Pavlov First Saint Petersburg State Medical University

编辑信件的主要联系方式.
Email: shcherbakns@yandex.ru
Russia, Saint Petersburg

G. Yukina

Pavlov First Saint Petersburg State Medical University

Email: shcherbakns@yandex.ru
Russia, Saint Petersburg

A. Gurbo

Pavlov First Saint Petersburg State Medical University

Email: shcherbakns@yandex.ru
Russia, Saint Petersburg

E. Sukhorukova

Pavlov First Saint Petersburg State Medical University

Email: shcherbakns@yandex.ru
Russia, Saint Petersburg

A. Sargsian

Pavlov First Saint Petersburg State Medical University

Email: shcherbakns@yandex.ru
Russia, Saint Petersburg

V. Thomson

Pavlov First Saint Petersburg State Medical University

Email: shcherbakns@yandex.ru
Russia, Saint Petersburg

参考

  1. Силькис И.Г. Механизмы функционирования коннектома, включающего неокортекс, гиппокамп, базальные ганглии, мозжечок и таламус. Журн. высш. нервн. деят. им. И.П. Павлова. 2022. 72 (1): 36–54.
  2. Сусликов В.Л., Толмачева Н.В., Александров Е.В. Анализ причинно-следственных связей феномена долгожительства. Вестн. Чувашского унив. 2013. 3: 531–539.
  3. Щербак Н.С., Кузьменко Н.В., Плисс М.Г. Влияние хлоралгидрата на показатели гемодинамики и поведенческие реакции у старых крыс. Рос. физиол. журн. им. И.М. Сеченова. 2019. 105 (7): 913–922. https://doi.org/10.1134/S0869813919070094
  4. Щербак Н.С., Юкина Г.Ю., Гурбо А.Г., Сухорукова Е.Г., Саргсян А.Г., Томсон В.В., Галагудза М.М. Морфофункциональное состояние микроглии и нейронов гиппокампа у возрастных крыс после анестезии хлоралгидратом. Регионарное кровообращение и микроциркуляция. 2022. 21 (3): 64–71. https://doi.org/10.24884/1682-6655-2022-21-3-64-71
  5. Щербак Н.С., Юкина Г.Ю., Сухорукова Е.Г., Томсон В.В. Влияние ишемического посткондиционирования на реакцию микроглии неокортекса при глобальной ишемии головного мозга у крыс. Регионарное кровообращение и микроциркуляция. 2020. 19 (2): 59–66. https://doi.org/10.24884/1682-6655-2020-19-2-59-66
  6. Юкина Г.Ю., Белозерцева И.В., Полушин Ю.С., Томсон В.В., Полушин А.Ю., Янишевский С.Н., Кривов В.О. Структурно-функциональная перестройка нейронов гиппокампа после операции под анестезией севофлураном (экспериментальное исследование). Вестник анестезиологии и реаниматологии. 2017. 14 (6): 65–72. https://doi.org/10.21292/2078-5658-2017-14-6-65-72
  7. Юкина Г.Ю., Сухорукова Е.Г., Белозерцева И.В., Полушин Ю.С., Томсон В.В., Полушин А.Ю. Реакция нейронов и микроглии коры мозжечка на анестезию севофлураном. Цитология. 2019. 61 (7): 548–555. https://doi.org/10.1134/S0041377119070101
  8. Ancelin M.L., de Roquefeuil G., Ledésert B., Bonnel F., Cheminal J.C., Ritchie K. Exposure to anaesthetic agents, cognitive functioning and depressive symptomatology in the elderly. Br J Psychiatry. 2001. 178: 360–366. https://doi.org/10.1192/bjp.178.4.360
  9. Barrientos R.M., Hein A.M., Frank M.G., Watkins L.R., Maier S.F. Intracisternal interleukin-1 receptor antagonist prevents postoperative cognitive decline and neuroinflammatory response in aged rats. J Neurosci. 2012. 32 (42): 14641–14648. https://doi.org/10.1523/JNEUROSCI.2173-12.2012
  10. Bayer S.A., Altman J., Russo R.J., Zhang X. Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. Neurotoxicology. 1993. 14 (1): 83–144.
  11. Bianchi S.L., Tran T., Liu C., Lin S., Li Y., Keller J.M., Eckenhoff R.G., Eckenhoff M.F. Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol Aging. 2008. 29 (7): 1002–1010. https://doi.org/10.1016/j.neurobiolaging.2007.-02.009
  12. Callaway J.K., Jones N.C., Royse A.G., Royse C.F. Sevoflurane anesthesia does not impair acquisition learning or memory in the Morris water maze in young adult and aged rats. Anesthesiology. 2012. 117: 1091–1101. https://doi.org/10.1097/ALN.0b013e31826cb228
  13. Cao K., Qiu L., Lu X., Wu W., Hu Y., Cui Z., Jiang C., Luo Y., Shao Y., Xi W., Zeng L.H., Xu H., Ma H., Zhang Z., Peng J., Duan S., Gao Z. Microglia modulate general anesthesia through P2Y12 receptor. Curr Biol. 2023. 33 (11): 2187–2200. e6. https://doi.org/10.1016/j.cub.2023.04.047
  14. Chen J., Sanberg P.R., Li Y., Wang L., Lu M., Willing A.E., Sanchez-Ramos J., Chopp M. Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke. 2001. 32 (11): 2682–2688. https://doi.org/10.1161/hs1101.098367
  15. Donkor E.S. “Stroke in the 21st century: A snapshot of the burden, epidemiology, and quality of life,” Stroke. Res. Treat. 2018. 3: 1–10. https://doi.org/10.1155/2018/3238165
  16. Dong Y., Zhang G., Zhang B., Moir R.D., Xia W., Marcantonio E.R., Culley D.J., Crosby G., Tanzi R.E., Xie Z. The common inhalational anesthetic sevoflurane induces apoptosis and increases beta-amyloid protein levels. Arch Neurol. 2009. 66 (5): 620–631. https://doi.org/10.1001/archneurol.2009.48
  17. Dubois B., Slachevsky A., Litvan I., Pillon B. The FAB: a Frontal Assessment Battery at bedside. Neurology. 2000. 55 (11): 1621–6. https://doi.org/10.1212/wnl.55.11.1621
  18. Farkas E., Luiten P.G.M., Bari F. Permanent, bilateral common carotid artery occlusion in the rat: A model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain research reviews. 2007. 54: 162–180. https://doi.org/10.1016/j.brainresrev.2007.01.003
  19. Gehrmann J., Bonnekoh P., Miyazawa T., Hossmann K.A., Kreutzberg G.W. Immunocytochemical study of an early microglial activation in ischemia. J Cereb Blood Flow Metab. 1992. 12 (2): 257–69. https://doi.org/10.1038/jcbfm.1992.36
  20. Hellwig S., Brioschi S., Dieni S., Frings L., Masuch A., Blank T., Biber K. Altered microglia morphology and higher resilience to stress-induced depression-like behavior in CX3CR1-deficient mice. Brain Behav Immun. 2016. 55: 126–137. https://doi.org/10.1016/j.bbi.2015.11.008
  21. Hofacer R.D., Deng M., Ward C.G., Joseph B., Hughes E.A., Jiang C., Danzer S.C., Loepke A.W. Cell age-specific vulnerability of neurons to anesthetic toxicity. Ann Neurol. 2013. 73 (6): 695–704. https://doi.org/10.1002/ana.23892
  22. Hovens I.B., van Leeuwen B.L., Nyakas C., Heineman E., van der Zee E.A., Schoemaker R.G. Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats. Neurobiol Learn Mem. 2015. 118: 74–79. https://doi.org/10.1016/j.nlm.2014.11.009
  23. Kirino T. Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 1982. 239: 57–69. https://doi.org/10.1016/0006-8993(82)90833-2
  24. Lee C.H., Yoo K.Y., Choi J.H., Park O.K., Hwang I.K., Kim S.K., Kang I.J., Kim Y.M., Won M.H. Neuronal damage is much delayed and microgliosis is more severe in the aged hippocampus induced by transient cerebral ischemia compared to the adult hippocampus. J. Neurol Sci. 2010. 294 (1–2): 1–6. https://doi.org/10.1016/j.jns.2010.04.014
  25. Liu J.H., Feng D., Zhang Y.F., Shang Y., Wu Y., Li X.F., Pei L. Chloral Hydrate Preconditioning Protects Against Ischemic Stroke via Upregulating Annexin A1. CNS Neurosci Ther. 2015. 21 (9): 718–726. https://doi.org/10.1111/cns.12435
  26. Moller J.T., Cluitmans P., Rasmussen L.S., Houx P., Rasmussen H., Canet J., Rabbitt P., Jolles J., Larsen K., Hanning C.D., Langeron O., Johnson T., Lauven P.M., Kristensen P.A., Biedler A., van Beem H., Fraidakis O., Silverstein J.H., Beneken J.E., Gravenstein J.S. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998. 251: 857–861. https://doi.org/10.1016/s0140-6736(97)07382-0
  27. Paolicelli R.C., Sierra A., Stevens B., Tremblay M.E., Aguzzi A., Ajami B., Amit I., Audinat E., Bechmann I., Bennett M., Bennett F., Bessis A., Biber K., Bilbo S., Blurton-Jones M., Boddeke E., Brites D., Brône B., Brown G.C., Butovsky O., Carson M.J., Castellano B., Colonna M., Cowley S.A., Cunningham C., Davalos D., De Jager P.L., de Strooper B., Denes A., Eggen B.J.L., Eyo U., Galea E., Garel S., Ginhoux F., Glass C.K., Gokce O., Gomez-Nicola D., González B., Gordon S., Graeber M.B., Greenhalgh A.D., Gressens P., Greter M., Gutmann D.H., Haass C., Heneka M.T., Heppner F.L., Hong S., Hume D.A., Jung S., Kettenmann H., Kipnis J., Koyama R., Lemke G., Lynch M., Majewska A., Malcangio M., Malm T., Mancuso R., Masuda T., Matteoli M., McColl B.W., Miron V.E., Molofsky A.V., Monje M., Mracsko E., Nadjar A., Neher J.J., Neniskyte U., Neumann H., Noda M., Peng B., Peri F., Perry V.H., Popovich P.G., Pridans C., Priller J., Prinz M., Ragozzino D., Ransohoff R.M., Salter M.W., Schaefer A., Schafer D.P., Schwartz M., Simons M., Smith C.J., Streit W.J., Tay T.L., Tsai L.H., Verkhratsky A., von Bernhardi R., Wake H., Wittamer V., Wolf S.A., Wu L.J., Wyss-Coray T. Microglia states and nomenclature: A field at its crossroads. Neuron. 2022. 110 (21): 3458–3483. https://doi.org/10.1016/j.neuron.2022.10.020
  28. Paxinos G., Watson Ch. The rat brain in stereotaxic coordinates. New York: Academic Press, 1998.
  29. Schaar K.L., Brenneman M.M., Savitz S.I. Functional assessments in the rodent stroke model. Exp Transl Stroke Med. 2010. 2 (1): 13. https://doi.org/10.1186/2040-7378-2-13
  30. Shcherbak N.S., Yukina G.Yu., Gurbo A.G., Sukhorukova E.G., Sargsian A.G., Barantsevich E.R., Thomson V.V., Galagudza M.M. Reaction of Microglia and Neurons of the Hippocampal CA1 Field to Chloral Hydrate in Old Rats. Advances in Gerontology. 2021. 11 (4): 341–345. https://doi.org/10.1134/S2079057021040123
  31. Stratmann G., Sall J.W., Bell J.S., Alvi R.S., May L.d., Ku B., Dowlatshahi M., Dai R., Bickler P.E., Russell I., Lee M.T., Hrubos M.W., Chiu C. Isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome in aged rats. Anesthesiology. 2010. 112 (2): 305–15. https://doi.org/10.1097/ALN.0b013e3181ca33a1
  32. Vachon P., Faubert S., Blais D., Comtois A., Bienvenu J.G. A pathophysiological study of abdominal organs following intraperitoneal injections of chloral hydrate in rats: comparison between two anaesthesia protocols. Lab Anim. 2000. 34 (1): 84–90. https://doi.org/10.1258/002367700780578082
  33. Wise S.P. Forward frontal fields: phylogeny and fundamental function. Trends Neurosci. 2008. 31 (12): 599–608. https://doi.org/10.1016/j.tins.2008.08.008
  34. Wu L., Zhao H., Weng H., Ma D. Lasting effects of general anesthetics on the brain in the young and elderly: “mixed picture” of neurotoxicity, neuroprotection and cognitive impairment. J Anesth. 2019. 33 (2): 321–335. https://doi.org/10.1007/s00540-019-02623-7
  35. Zhen Y., Dong Y., Wu X., Xu Z., Lu Y., Zhang Y., Norton D., Tian M., Li S., Xie Z. Nitrous oxide plus isoflurane induces apoptosis and increases beta-amyloid protein levels. Anesthesiology. 2009. 111 (4): 741–752. https://doi.org/10.1097/ALN.0b013e3181b27fd4

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版权所有 © Н.С. Щербак, Г.Ю. Юкина, А.Г. Гурбо, Е.Г. Сухорукова, А.Г. Саргсян, В.В. Томсон, 2023

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