Methodological study investigating long term laser Doppler measured cerebral blood flow changes in a permanently occluded rat stroke model

Eve, David J.; Musso, James; Park, Dong Hyuk; Oliveira, Cathy; Pollock, Kenny; Hope, Andrew; Baradez, Marc‐Olivier; Sinden, John D.; Sanberg, Paul R.

doi:10.1016/j.jneumeth.2009.02.016

Cited by 7 publications

(8 citation statements)

References 24 publications

(38 reference statements)

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“…Both techniques have been validated for the study of focal ischemia in rodents (Bratane et al, 2010). Arterial spin labeling (Jiang et al, 1998) and dynamic susceptibility contrast MRI (Rudin et al, 2001;Lin et al, 2008) have shown prolonged cortical and striatal hypoperfusion after permanent middle cerebral artery occlusion in rats, which is consistent with studies using autoradiography or laser Doppler flowmetry (Bolander et al, 1989;Borlongan et al, 2004;Li et al, 2007;Eve et al, 2009). Relatively few studies have looked beyond the first few days after injury and at regions outside the primary infarct, although knowledge of how the cerebral blood supply adapts long after ischemic injury may aid our understanding of brain recovery processes.…”

Section: Introductionmentioning

confidence: 56%

“…This hypoperfusion resolved by 28 days after ischemia, which may be due to the establishment of collateral blood supply. More recently, laser Doppler flowmetry has shown that periinfarct hypoperfusion prevails for several weeks after permanent (Eve et al, 2009) and transient (Borlongan et al, 2004) middle cerebral artery occlusion in rats. Dynamic susceptibility contrast MRI has shown that hypoperfusion prevails for at least 3 days in the ipsilateral striatum (Rudin et al, 2001) and up to 14 days in the ipsilateral cortex (Lin et al, 2002).…”

Section: Hypoperfusion At the Acute Phase In The Cortex And Thalamus mentioning

confidence: 99%

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Chronic Hyperperfusion and Angiogenesis Follow Subacute Hypoperfusion in the Thalamus of Rats with Focal Cerebral Ischemia

Hayward

Yanev

Haapasalo

et al. 2010

J Cereb Blood Flow Metab

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Cerebral blood flow (CBF) is disrupted after focal ischemia in rats. We examined long-term hemodynamic and cerebrovascular changes in the rat thalamus after focal cerebral ischemia. Cerebral blood flow quantified by arterial spin labeling magnetic resonance imaging was decreased in the ipsilateral and contralateral thalamus 2 days after cerebral ischemia. Partial thalamic CBF recovery occurred by day 7, then the ipsilateral thalamus was chronically hyperperfused at 30 days and 3 months compared with its contralateral side. This contrasted with permanent hypoperfusion in the ipsilateral cortex. Angiogenesis was indicated by endothelial cell (RECA-1) immunohistochemistry that showed increased blood vessel branching in the ipsilateral thalamus at the end of the 3-month follow-up. Only transient thalamic IgG extravasation was observed, indicating that the blood-brain barrier was intact after day 2. Angiogenesis was preceded by transiently altered expression levels of cadherin family adhesion molecules, cadherin-7, protocadherin-1, and protocadherin-17. In conclusion, thalamic pathology after focal cerebral ischemia involved longterm hemodynamic changes and angiogenesis preceded by altered expression of vascular adhesion factors. Postischemic angiogenesis in the thalamus represents a novel type of remote plasticity, which may support removal of necrotic brain tissue and aid functional recovery.

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Section: Introductionmentioning

confidence: 56%

Section: Hypoperfusion At the Acute Phase In The Cortex And Thalamus mentioning

confidence: 99%

Chronic Hyperperfusion and Angiogenesis Follow Subacute Hypoperfusion in the Thalamus of Rats with Focal Cerebral Ischemia

Hayward

Yanev

Haapasalo

et al. 2010

J Cereb Blood Flow Metab

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“…Implanted CTX cells were also found to increase CBF on the lesioned side in MCAo-lesioned rats [82]. PET studies indicate that there is a significant ischemic penumbra in humans, and that reversibly, ischemic tissue may persist for much longer than the initial experiments in animal models have suggested [83].…”

Section: Mechanisms Of Action Of Hnscs In Ischemic Strokementioning

confidence: 99%

“…However, Ulrich et al [88] followed CBF for 3 and 6 weeks after permanent MCAo and did not see a complete return to normal levels. Eve et al [82], after examining both hemispheres, noted a difference in CBF between the left and right sides and a shifting in direction in a visual oscillatory fashion over time in control, sham-occluded, rats. This change in dominance between the left and right CBF suggested a natural oscillation of CBF in normal animals.…”

Section: Mechanisms Of Action Of Hnscs In Ischemic Strokementioning

confidence: 99%

“…In occluded animals, the laser Doppler measurements of CBF showed consistent left-side dominance. By 3 months after implantation, the CBF was observed to have improved in the lesioned hemisphere of the CTX-treated group compared with the untreated stroke rats and demonstrated a similar oscillatory nature as that seen in sham-occluded animals [82]. …”

Section: Mechanisms Of Action Of Hnscs In Ischemic Strokementioning

confidence: 99%

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Human Neural Stem Cell Therapy for Chronic Ischemic Stroke: Charting Progress from Laboratory to Patients

SindenJohn

HicksCaroline

StroemerPaul

et al. 2017

Stem Cells and Development

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Chronic disability after stroke represents a major unmet neurologic need. ReNeuron's development of a human neural stem cell (hNSC) therapy for chronic disability after stroke is progressing through early clinical studies. A Phase I trial has recently been published, showing no safety concerns and some promising signs of efficacy. A single-arm Phase II multicenter trial in patients with stable upper-limb paresis has recently completed recruitment. The hNSCs administrated are from a manufactured, conditionally immortalized hNSC line (ReNeuron's CTX0E03 or CTX), generated with c-mycERTAM technology. This technology has enabled CTX to be manufactured at large scale under cGMP conditions, ensuring sufficient supply to meets the demands of research, clinical development, and, eventually, the market. CTX has key pro-angiogenic, pro-neurogenic, and immunomodulatory characteristics that are mechanistically important in functional recovery poststroke. This review covers the progress of CTX cell therapy from its laboratory origins to the clinic, concluding with a look into the late stage clinical future.

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Optical monitoring of cerebral microcirculation in neurointensive care

Rejmstad

Haj‐Hosseini

Åneman

et al. 2017

Med Biol Eng Comput

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Continuous optical monitoring of local cerebral microcirculation could benefit neurointensive care patients treated for subarachnoid hemorrhage (SAH). The aim of the study was to evaluate laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) for long-term monitoring of brain microcirculation and oxygen saturation (SO2) in the neurointensive care unit (NICU). A fiber optic probe was designed for intraparenchymal use and connected to LDF and DRS for assessment of the local blood flow (perfusion and tissue reflectance (TLI)) and SO2 in the brain. The optically monitored parameters were compared with conventional NICU monitors and Xe-CT. The LDF signals were low with median and 25 to 75% interquartiles of perfusion = 70 (59 to 83) a.u. and TLI = 2.0 (1.0 to 2.4) a.u. and showed correlation with the NICU monitors in terms of heart rate. Median and interquartiles of SO2 were 17.4 (15.7 to 19.8) %. The lack of correlation between local perfusion and cerebral perfusion pressure indicated intact cerebral autoregulation. The systems were capable of monitoring both local perfusion and SO2 with stable signals in the NICU over 4 days. Further clinical studies are required to evaluate the optical systems’ potential for assessing the onset of secondary brain injury.

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Methodological study investigating long term laser Doppler measured cerebral blood flow changes in a permanently occluded rat stroke model

Cited by 7 publications

References 24 publications

Chronic Hyperperfusion and Angiogenesis Follow Subacute Hypoperfusion in the Thalamus of Rats with Focal Cerebral Ischemia

Chronic Hyperperfusion and Angiogenesis Follow Subacute Hypoperfusion in the Thalamus of Rats with Focal Cerebral Ischemia

Human Neural Stem Cell Therapy for Chronic Ischemic Stroke: Charting Progress from Laboratory to Patients

Optical monitoring of cerebral microcirculation in neurointensive care

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