Single photon emission computed tomography imaging of cerebral blood flow, blood–brain barrier disruption, and apoptosis time course after focal cerebral ischemia in rats

By following up on this in humans we should be able to calculate the numbers of neurons dying during the neuronal cascade of death in the first week. We already know that 1.9 million die per minute during the actual stroke, which leads to the mantra, 'Time is Brain'. We've known this for ten years and yet our fucking failures of stroke associations have done nothing in those ten years to solve anything in stroke. How many gazillions of dead neurons are our stroke associations responsible for killing?  If we can come up with the number dying the first week we might have a chance of actually getting researchers to solve the problem of stopping the 5 causes of neuronal death. But since we have NO stroke strategy or stroke leadership in any part of stroke no will even attempt to solve this. Your children and grandchildren are fucking screwed if they have a stroke since nothing will be done better than today.
http://wso.sagepub.com/content/11/1/117.abstract?

1. Philippe Garrigue1,2,3
2. Laura Giacomino4
3. Chiara Bucci5
4. Valeria Muzio5
5. Maria A Filannino5
6. Florence Sabatier1,6
7. Françoise Dignat-George1,7
8. Pascale Pisano1,8
9. Benjamin Guillet1,2,3⇑

1. ¹INSERM, INSERM UMR_S1076 VRCM Aix-Marseille Université, France
2. ²APHM, Hôpital La Timone, Service de Radiopharmacie, Marseille, France
3. ³CERIMED, Aix-Marseille Université, Marseille, France
4. ⁴Département Anesthésie-Réanimation adulte, APHM, Aix-Marseille Université, Marseille, France
5. ⁵Advanced Accelerator Applications, Colleretto Giacosa (TO), Italy
6. ⁶APHM, Laboratoire de Culture et Thérapie Cellulaire, INSERM, Hôpital La Conception, Marseille, France
7. ⁷APHM, Hôpital La Conception, Service d’Hématologie, Marseille, France
8. ⁸APHM, Pôle Pharmacie, Marseille, France

1. Benjamin Guillet, Faculté de Pharmacie, 27 Bd Jean Moulin, 13005 Marseille, France. Email: benjamin.guillet@univ-amu.fr

Abstract

Background Cerebral ischemia is a leading cause of disability worldwide and no other effective therapy has been validated to date than intravenous thrombolysis. In this context, many preclinical models have been developed and recent advances in preclinical imaging represent promising tools. Thus, we proposed here to characterize in vivo time profiles of cerebral blood flow, blood–brain barrier disruption and apoptosis following a transient middle cerebral artery occlusion in rats using SPECT/CT imaging.

Methods Rats underwent a 1-h middle cerebral artery occlusion followed by reperfusion. Cerebral blood flow, blood–brain barrier disruption and apoptosis were evaluated by SPECT/CT imaging using respectively ^99mTc-HMPAO, ^99mTc-DTPA and the experimental ^99mTc-Annexin V-128, up to 14 days after middle cerebral artery occlusion. Histological evaluation of apoptosis has been performed using TUNEL method to validate the ^99mTc-Annexin V-128 uptake.

Results ^99mTc-HMPAO cerebral blood flow evaluation showed hypoperfusion during occlusion, partially restored on days 4 and 7 and sustained up to 14 days after middle cerebral artery occlusion. ^99mTc-DTPA SPECT/CT showed a blood–brain barrier disruption starting on day 1 post-middle cerebral artery occlusion, peaking on day 2, with barrier integrity totally restored on day 7. ^99mTc-Annexin V-128 SPECT/CT imaging showed significant positive correlation with TUNEL immunohistochemistry and allowed ischemic-induced apoptosis to be detected from day 2 to day 7, peaking on day 3 after middle cerebral artery occlusion.

Conclusions Using SPECT/CT imaging, we showed that after transient middle cerebral artery occlusion in rat there was a sustained decrease in cerebral blood flow followed by blood–brain barrier disruption preceding meanwhile apoptosis. Rodent SPECT/CT imaging of cerebral blood flow, blood–brain barrier disruption and apoptosis appears to be an efficient tool for evaluating neuroprotective drugs and regenerative therapies against cerebral ischemia and time-windows for therapeutic intervention.