Histopathological Investigation of Different MCAO Modalities and Impact of Autologous Bone Marrow Mononuclear Cell Administration in an Ovine Stroke Model
Johannes Boltze,Johannes Boltze,Björn Nitzsche,Björn Nitzsche,Björn Nitzsche,Kathrin Geiger,Heinz-Adolf Schoon +6 more
TLDR
The sheep model may represent a feasible tool for translational stroke research as pathohistological findings mimic the situation in humans.Abstract:
Translational researchers and clinicians recommend the use of large animal models in preclinical stroke research. This represents an important part of a strategy aiming to prevent past translational failures in future therapeutic developments. Thirty-five Merino rams were subjected to sham surgery (n = 3), one-branch middle cerebral artery occlusion (MCAO, n = 8) or total MCAO (n = 24). Twelve animals from the latter group received intravenous administration of 4 × 106 autologous mononuclear bone marrow cells (BM MNC) per kilogram 24 h after total MCAO. Animals were sacrificed at day 49 post MCAO. Histological investigations were performed to reveal (1) the impact of different MCAO modalities on a cellular level and (2) the influence of BM MNC therapy following stroke. Clear differences between one-branch and total MCAO were observed histologically with results being comparable to those seen in human patients. BM MNC treatment reduced final lesion extension, lymphocytic infiltration and axonal degeneration after MCAO. The sheep model may represent a feasible tool for translational stroke research as pathohistological findings mimic the situation in humans. Histological evidence was found for beneficial impact of autologous BM MNC therapy. Further studies are needed to assess the neurofunctional impact of the approach in the gyrencephalic brain.read more
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Bone marrow mononuclear cells promote proliferation of endogenous neural stem cells through vascular niches after cerebral infarction
Akiko Doi,Takayuki Nakagomi,Nami Nakagomi,Orie Saino,Masashi Takata,Shan Lu,Hisao Tachibana,Akihiko Taguchi,Tomohiro Matsuyama +8 more
TL;DR: BMMCs target vascular niche at first, and then contribute to the proliferation of endogenous ischemia-induced NSPs through upregulation of endothelial proliferative activity, suggesting that BMMCs transplantation is a novel therapeutic option in stroke treatment.
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Translational models for vascular cognitive impairment: a review including larger species
Atticus H. Hainsworth,Atticus H. Hainsworth,Stuart M. Allan,Johannes Boltze,Johannes Boltze,Catriona J Cunningham,Chad Farris,Elizabeth Head,Masafumi Ihara,Jeremy D. Isaacs,Jeremy D. Isaacs,Raj N. Kalaria,Saskia A J Lesnik Oberstein,Mark B. Moss,Björn Nitzsche,Björn Nitzsche,Gary A. Rosenberg,Julie W. Rutten,Melita Salkovic-Petrisic,Aron M. Troen +19 more
TL;DR: It is concluded that translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; rodent models of VCI are limited by paucity of white matter; and further translational Models, and improved cognitive testing instruments, are required.
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Large animal models of stroke and traumatic brain injury as translational tools.
TL;DR: An overview of large animal models of TBI and ischemic stroke, including the surgical considerations, key benefits, and limitations of each approach are provided.
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Correcting for Brain Swelling’s Effects on Infarct Volume Calculation After Middle Cerebral Artery Occlusion in Rats
TL;DR: This algorithm offers a more reliable estimation of the infarct volume after ischemic brain injury, and thus may provide the foundation for comparinginfarct volumes between experimental studies and standardizing infarCT volume quantification to aid in the selection of the best candidates for clinical trials.
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