Ischemia-reperfusion injury:
Recent clinical data challenge the translational value of mechanical MCAO models of stroke in rodents



Ischemia-reperfusion injury has been hypothesized to play a major role in the physiopathology of acute stroke since it has been demonstrated that abrupt reperfusion induces secondary brain damages responsible for up to 70% of the final ischemic lesion size in rodents.

However, such a critical role for abrupt reperfusion on the ischemic injury has never been clearly demonstrated in human. Indeed, clinical data were still lacking up to recently. It is of importance considering that mechanical ischemia-reperfusion with a monofilament has been considered as a gold-standard model of stroke for decades.


That’s why Strok@lliance‘s academic partner (PhIND laboratory, Caen) reanalysed data from Aspiration vs Stent Retriever for Successful Revascularization (ASTER) clinical study to evaluate cerebral infarct progression after abrupt reperfusion in thrombectomised patients.

The results, recently published in the journal Stroke, did not evidence any lesion growth 24h after complete reperfusion in most patients.


This discrepancy between clinical and preclinical pathophysiologies question the translational value of the mechanical ischemia-reperfusion model in rodents and should be considered during preclinical evaluation of neuroprotective strategies. In particular, it indicates that this model is not a translational model of thrombectomy nor a suitable model to test neuroprotective agent efficacy during the acute phase of stroke.

It underlines the urgent need for more translational models. That’s why we, at Strok@lliance, are committed to provide innovative ischemic stroke models to support the development of new drugs.


Link toward the article

2018 has been a rewarding year for Strok@lliance as a result of several projects completed and new models that have been developed! Here is a brief summary of the key points regarding our development and achievements:

  • Strok@lliance is proud to count new clients from mid-size to top 10 pharma companies.
  • Several new tailor-made models have been added to our catalogue according to customers request including:

→ A double autologous blood injection in cisterna magna, a complex model of subarachnoidian hemorrhage in rat.

→ Models of ischemia-reperfusion in juvenile rats (28 days) enabling Strok@lliance to predict the effects related to drug administration on children.

  • Strok@lliance obtained a grant from French research ministry to start a CIFRE Thesis. The Thesis will start in spring 2019 and will focused on the refinement of our thrombin-induced stroke models by the addition of comorbidities (aging, hypertension, diabetes…).
  • Strok@lliance team is growing with the recruitment of new technicians, empowering us to carry out more and more projects with the same level of quality and efficiency.

After these past two years, Strok@lliance is pursuing its objective of becoming a reference as the preclinical CRO dedicated to stroke with an increasingly number of projects planned for 2019.

Our team is grateful for the trust customers placed in us to design and validate stroke models, as well as to carry out their pre-clinical studies. We are committed to provide services of quality and are constantly evolving to answer customer specific demands.

Strok@lliance is pleased to announce the acquisition of ISO 9001 certification based on the standard from 2015.

Through an internal and external Audit of the OFC (the French Certification Organization): quality assurance, control and monitoring procedures have been carried out to attest to the quality of our services.

By being accredited, our company is insuring the customers to meet their expectations by the quality of its management system in the following areas: consulting, advising and expertise of studies in the field of in vitro and in vivo preclinical research.

A very interesting review have been published by our Caen academic partner (PhIND unit, Université de Caen Normandie / INSERM ) concerning the current evidence linking tPA mediated thrombolysis, bradykinin generation and potential subsequent neurovascular damages. While tPA is an important pharmacological tool for acute stroke management, this clot buster also promotes hemorrhagic transformation, symptomatic cerebral edema and angioedema. Preclinical and clinical evidence suggests that intravenous thrombolysis generates large amounts of bradykinin, a peptide with potent pro-inflammatory, and pro-edematous effects. Thus, this tPA-induced generation of bradykinin is a potential target to improve neurological outcome after thrombolysis.

Link to the article

JOIN US!

 

Strok@lliance is growing to provide its customers with high level and original services in preclinical stroke studies.

You have now the opportunity to join a young and dynamic team looking for challenge in a high level scientific and technologic environment !

 

Strok@lliance invites applications from eligible candidates for recruitment of a Scientific Laboratory Technician in stroke preclinical testing.

The company is looking for individuals who wants to contribute their skills to provide excellent work in a challenging and rewarding environment.

 

Find the application details here.