Mesenchymal stem cells (MSC) were reported to ameliorate functional deficits after stroke in rats, with some of this improvement possibly resulting from the action of cytokines secreted by these cells. To enhance such cytokine effects, we previously transfected the telomerized human MSC with the BDNF gene using a fiber-mutant adenovirus vector and reported that such treatment contributed to improved ischemic recovery in a rat transient middle cerebral artery occlusion (MCAO) model. In the present study, we investigated whether other cytokines in addition to BDNF, i.e., GDNF, CNTF, or NT3, might have a similar or greater effect in this model. Rats that received MSC-BDNF (P < 0.05) or MSC-GDNF (P < 0.05) showed significantly more functional recovery as demonstrated by improved behavioral test results and reduced ischemic damage on MRI than did control rats 7 and 14 days following MCAO. On the other hand, rats that received MSC-CNTF or MSC-NT3 showed neither functional recovery nor ischemic damage reduction compared to control rats. Thus, MSC transfected with the BDNF or GDNF gene resulted in improved function and reduced ischemic damage in a rat model of MCAO. These data suggest that gene-modified cell therapy may be a useful approach for the treatment of stroke.
Enthalpic path and enthalpy-relaxation rates of ethylbenzene glasses prepared by vapor deposition at various temperatures, T(D), were examined on heating intermittently with a high-precision adiabatic calorimeter. It was confirmed that when T(D) is in the range 0.79-0.96T(g), the enthalpies elucidated at their preparation temperatures, i.e., T(D), are lower than those of the liquid-cooled glass. The fictive temperature T(f) at which the enthalpy path of each glass crosses the enthalpy curve expected for the equilibrium supercooled liquid was observed to be lowest when T(D) = 0.92T(g) = 105 K. The glasses revealed two remarkable characteristics: first, the temperature of the peak in the endothermic effect, which corresponds to the temperature T(g,dev) of the steepest devitrification, was observed to increase in correlation with the low-enthalpic nature of the glasses. Second, the devitrification manner was quite different between the glasses with T(D) < 0.92T(g) and T(D) ≥ 0.92T(g), even if the two glasses have the same T(f); the former devitrified gradually and the latter relatively sharply.
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