Morphological characteristic of intracerebral hemorrhage in rats and correlation of its volume with results of behavioral tests

Authors

DOI:

https://doi.org/10.25305/unj.221282

Keywords:

intracerebral hemorrhage, rats, behavioral tests, morphometry

Abstract

The intracerebral hemorrhage is associated with severe complications and high mortality. Currently there are no effective methods of treatment of this disease while the standard collagenase model of intracerebral hemorrhage is not described sufficiently.

Objective. To analyze morphological characteristics of the collagenase model of intracerebral hemorrhage, and develop the regression formula predicting the hemorrhage volume based on the results of behavioral tests.

Materials and methods. The experiments were carried out on 7 white male rats weighing 250-400 g aged 11-13 months. All animals underwent surgery to simulate intracerebral hemorrhage. Rats were anesthetized and then, stereotactically, using a needle with a diameter of 0.47 mm, 0.2 units of collagenase type IV were slowly injected into the left striatum. The day after the intracerebral hemorrhage, functional disabilities developed in rats were studied using beam walking test, neurological score test and adhesive removal test. Immediately after performing behavioral tests, the rats were sacrificed by decapitation. After the brain formalin fixation, serial sections on a vibromicrotome of 200 µm thick each in the anteroposterior direction with following morphological examination were made.

Results. It was revealed that the collagenase model of intracerebral hemorrhage is associated with a large variability of the hemorrhage volume. It also had an irregular rugged shape and marks of repeated diapedetic hemorrhages of about 0.6 mm depth. The center of intracerebral hemorrhage along the anteroposterior axis was in average 0.5 mm posterior of the actual site of collagenase injection.
The combined use of the neurological score test, the beam walking test and the adhesive removal test in the collagenase model can help estimate the probable intracerebral hemorrhage volume on the 1st day using the regression formula.

Conclusions. Technical details identified in our study can help researchers in planning and conduction of correct experiments related to intracerebral hemorrhage.

Author Biographies

Kyrylo M. Zolotko, Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkiv, Ukraine

Department of Cryoprotectants

 

Oleksandr M. Sukach, Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkiv, Ukraine; H.S. Skovoroda Kharkiv National Pedagogical University, Kharkiv, Ukraine

Department of Cryobiochemistry; Ya.R. Sinelnikov Department of Human Anatomy and Physiology

Antonina M. Kompaniiets, Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkiv, Ukraine

Department of Cryoprotectants

Kateryna S. Liubomudrova, Kharkiv National Medical University, Kharkiv, Ukraine

Department of the Clinical Anatomy and Operative Surgery

References

1. An SJ, Kim TJ, Yoon BW. Epidemiology, Risk Factors, and Clinical Features of Intracerebral Hemorrhage: An Update. J Stroke. 2017 Jan;19(1):3-10. [CrossRef] [PubMed] [PubMed Central]

2. Godoy DA, Núñez-Patiño RA, Zorrilla-Vaca A, Ziai WC, Hemphill JC. Intracranial Hypertension After Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis of Prevalence and Mortality Rate. Neurocrit Care. 2019 Aug;31(1):176-87. [CrossRef] [PubMed]

3. Fiorella D, Zuckerman SL, Khan IS, Ganesh Kumar N, Mocco J. Intracerebral Hemorrhage: A Common and Devastating Disease in Need of Better Treatment. World Neurosurg. 2015 Oct;84(4):1136-41. [CrossRef] [PubMed]

4. MacLellan CL, Silasi G, Poon CC, Edmundson CL, Buist R, Peeling J, Colbourne F. Intracerebral hemorrhage models in rat: comparing collagenase to blood infusion. J Cereb Blood Flow Metab. 2008 Mar;28(3):516-25. [CrossRef] [PubMed]

5. Sang YH, Liang YX, Liu LG, Ellis-Behnke RG, Wu WT, So KF, Cheung RT. Rat model of intracerebral hemorrhage permitting hematoma aspiration plus intralesional injection. Exp Anim. 2013;62(1):63-9. [CrossRef] [PubMed]

6. Paxions G, Watson C. The rat brain in stereotaxic coordinates: Compact. 7th ed. Sydney: Academic Press; 2017. 388p.

7. Beray-Berthat V, Delifer C, Besson VC, Girgis H, Coqueran B, Plotkine M, Marchand-Leroux C, Margaill I. Long-term histological and behavioural characterisation of a collagenase-induced model of intracerebral haemorrhage in rats. J Neurosci Methods. 2010 Aug 30;191(2):180-90. [CrossRef] [PubMed]

8. Urakawa S, Hida H, Masuda T, Misumi S, Kim TS, Nishino H. Environmental enrichment brings a beneficial effect on beam walking and enhances the migration of doublecortin-positive cells following striatal lesions in rats. Neuroscience. 2007 Feb 9;144(3):920-33. [CrossRef] [PubMed]

9. Ross MH. Histology: a text and atlas with correlated cell and molecular biology. 7th ed. 2016. 984 p.

10. Kvitnitskaia-Ryzhkova TYu, Bozhok YuM, editors. Introduction to quantitative histology. Kiev: Kniga-plus; 2013. 256 p. Russian.

11. Artamentova LO, Utevska OM. Statistics for biologists. Kharkiv: HTMT; 2014. 331 p. Ukrainian.

12. McDonald JH. Handbook of biological statistics. Baltimore: Sparky House Publishing; 2014. 299 p.

13. Perry LA, Rodrigues M, Al-Shahi Salman R, Samarasekera N. Incident cerebral microbleeds after intracerebral hemorrhage. Stroke. 2019 Aug;50(8):2227-2230. [CrossRef] [PubMed]

14. Tao Y, Tang J, Chen Q, Guo J, Li L, Yang L, Feng H, Zhu G, Chen Z. Cannabinoid CB2 receptor stimulation attenuates brain edema and neurological deficits in a germinal matrix hemorrhage rat model. Brain Res. 2015 Mar 30;1602:127-35. [CrossRef] [PubMed]

15. Kitaoka T, Hua Y, Xi G, Hoff JT, Keep RF. Delayed argatroban treatment reduces edema in a rat model of intracerebral hemorrhage. Stroke. 2002 Dec;33(12):3012-8. [CrossRef] [PubMed]

16. Klahr AC, Dietrich K, Dickson CT, Colbourne F. Prolonged Localized Mild Hypothermia Does Not Affect Seizure Activity After Intracerebral Hemorrhage in Rats. Ther Hypothermia Temp Manag. 2016 Mar;6(1):40-7. [CrossRef] [PubMed]

17. Klahr AC, Dickson CT, Colbourne F. Seizure activity occurs in the collagenase but not the blood infusion model of striatal hemorrhagic stroke in rats. Transl Stroke Res. 2015 Feb;6(1):29-38. [CrossRef] [PubMed] [PubMed Central]

Downloads

Published

2021-03-29

How to Cite

Zolotko, K. M., Sukach, O. M. ., Kompaniiets, A. M., & Liubomudrova, K. S. (2021). Morphological characteristic of intracerebral hemorrhage in rats and correlation of its volume with results of behavioral tests. Ukrainian Neurosurgical Journal, 27(1), 21–28. https://doi.org/10.25305/unj.221282

Issue

Section

Original articles