A review of experimental models of focal cerebral ischemia focusing on the middle cerebral artery occlusion model
Copyright: © 2021 Trotman-Lucas M and Gibson CL..
Cerebral ischemic stroke is a leading cause of death and disability, but current pharmacological therapies are limited in their utility and effectiveness. In vitro and in vivo models of ischemic stroke have been developed which allow us to further elucidate the pathophysiological mechanisms of injury and investigate potential drug targets. In vitro models permit mechanistic investigation of the biochemical and molecular mechanisms of injury but are reductionist and do not mimic the complexity of clinical stroke. In vivo models of ischemic stroke directly replicate the reduction in blood flow and the resulting impact on nervous tissue. The most frequently used in vivo model of ischemic stroke is the intraluminal suture middle cerebral artery occlusion (iMCAO) model, which has been fundamental in revealing various aspects of stroke pathology. However, the iMCAO model produces lesion volumes with large standard deviations even though rigid surgical and data collection protocols are followed. There is a need to refine the MCAO model to reduce variability in the standard outcome measure of lesion volume. The typical approach to produce vessel occlusion is to induce an obstruction at the origin of the middle cerebral artery and reperfusion is reliant on the Circle of Willis (CoW). However, in rodents the CoW is anatomically highly variable which could account for variations in lesion volume. Thus, we developed a refined approach whereby reliance on the CoW for reperfusion was removed. This approach improved reperfusion to the ischemic hemisphere, reduced variability in lesion volume by 30%, and reduced group sizes required to determine an effective treatment response by almost 40%. This refinement involves a methodological adaptation of the original surgical approach which we have shared with the scientific community via publication of a visualised methods article and providing hands-on training to other experimental stroke researchers.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
F1000Research - 10(2021) vom: 01., Seite 242 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Trotman-Lucas, Melissa [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Focal ischemia |
|---|
| Anmerkungen: |
Date Completed 27.07.2021 Date Revised 27.07.2021 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.12688/f1000research.51752.2 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM325949131 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM325949131 | ||
| 003 | DE-627 | ||
| 005 | 20231225195938.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.12688/f1000research.51752.2 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1090.xml |
| 035 | |a (DE-627)NLM325949131 | ||
| 035 | |a (NLM)34046164 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Trotman-Lucas, Melissa |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A review of experimental models of focal cerebral ischemia focusing on the middle cerebral artery occlusion model |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.07.2021 | ||
| 500 | |a Date Revised 27.07.2021 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright: © 2021 Trotman-Lucas M and Gibson CL. | ||
| 520 | |a Cerebral ischemic stroke is a leading cause of death and disability, but current pharmacological therapies are limited in their utility and effectiveness. In vitro and in vivo models of ischemic stroke have been developed which allow us to further elucidate the pathophysiological mechanisms of injury and investigate potential drug targets. In vitro models permit mechanistic investigation of the biochemical and molecular mechanisms of injury but are reductionist and do not mimic the complexity of clinical stroke. In vivo models of ischemic stroke directly replicate the reduction in blood flow and the resulting impact on nervous tissue. The most frequently used in vivo model of ischemic stroke is the intraluminal suture middle cerebral artery occlusion (iMCAO) model, which has been fundamental in revealing various aspects of stroke pathology. However, the iMCAO model produces lesion volumes with large standard deviations even though rigid surgical and data collection protocols are followed. There is a need to refine the MCAO model to reduce variability in the standard outcome measure of lesion volume. The typical approach to produce vessel occlusion is to induce an obstruction at the origin of the middle cerebral artery and reperfusion is reliant on the Circle of Willis (CoW). However, in rodents the CoW is anatomically highly variable which could account for variations in lesion volume. Thus, we developed a refined approach whereby reliance on the CoW for reperfusion was removed. This approach improved reperfusion to the ischemic hemisphere, reduced variability in lesion volume by 30%, and reduced group sizes required to determine an effective treatment response by almost 40%. This refinement involves a methodological adaptation of the original surgical approach which we have shared with the scientific community via publication of a visualised methods article and providing hands-on training to other experimental stroke researchers | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Stroke | |
| 650 | 4 | |a focal ischemia | |
| 650 | 4 | |a in vivo | |
| 650 | 4 | |a ischemia | |
| 650 | 4 | |a refinement | |
| 700 | 1 | |a Gibson, Claire L |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t F1000Research |d 2012 |g 10(2021) vom: 01., Seite 242 |w (DE-627)NLM22994549X |x 2046-1402 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2021 |g day:01 |g pages:242 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.12688/f1000research.51752.2 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2021 |b 01 |h 242 | ||