Background and Purpose
Remote ischemic conditioning is cardioprotective in myocardial infarction and neuroprotective in mechanical occlusion models of stroke. However, there is no report on its therapeutic potential in a physiologically relevant embolic stroke model (eMCAO) in combination with intravenous (IV) tissue plasminogen activator (tPA).
Methods
We tested remote ischemic perconditioning therapy (RIPerC) at 2 hours after eMCAO in the mouse with and without IV tPA at 4 hours. We assessed cerebral blood flow (CBF) up to 6 hours, neurologic deficits, injury size and phosphorylation of Akt (Serine473; p-Akt) as a pro-survival signal in the ischemic hemisphere at 48 hours post stroke.
Results
RIPerC therapy alone improved the CBF and neurologic outcomes. tPA alone at 4 hours did not significantly improve the neurologic outcome even after successful thrombolysis. Individual treatments with RIPerC and IV tPA reduced the infarct size (25.7% and 23.8%, respectively). Combination therapy of RIPerC and tPA resulted in additive effects in further improving the neurologic outcome, and reducing the infarct size (50%). All the therapeutic treatments upregulated p-Akt in the ischemic hemisphere.
Conclusions
RIPerC is effective alone after eMCAO and has additive effects in combination with IV tPA. RIPerC may be a simple, safe and inexpensive combination therapy with IV tPA.
Age-dependent bone loss has been well documented in both human and animal models. Although the underlying causal mechanisms are probably multifactorial, it has been hypothesized that alterations in progenitor cell number or function are important. Little is known regarding the properties of bone marrow stromal cells (BMSCs) or bone progenitor cells during the aging process, so the question of whether aging alters BMSC/progenitor osteogenic differentiation remains unanswered. In this study, we examined agedependent changes in bone marrow progenitor cell number and differentiation potential between mature (3 and 6 mo old), middle-aged (12 and 18 mo old), and aged (24 mo old) C57BL/6 mice. BMSCs or progenitors were isolated from five age groups of C57BL/6 mice using negative immunodepletion and positive immunoselection approaches. The osteogenic differentiation potential of multipotent BMSCs was determined using standard osteogenic differentiation procedures. Our results show that both BMSC/progenitor number and differentiation potential increase between the ages of 3 and 18 mo and decrease rapidly thereafter with advancing age. These results are consistent with the changes of the mRNA levels of osteoblast lineageassociated genes. Our data suggest that the decline in BMSC number and osteogenic differentiation capacity are important factors contributing to age-related bone loss.
Intraovarian administered BMSCs are able to restore ovarian hormone production and reactivate folliculogenesis in chemotherapy-induced ovarian failure mouse model.
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