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Diffusion tensor (DT) imaging measures the random molecular diffusion of water in vivo and provides information on the microstructure of tissue. Ischemic brain damage leads to tissue disorganization and structural lost. We aimed to evaluate these changes in a rat model of focal stroke from the hyperacute to chronic phase by utilizing several DT indices. Adult male Wistar rats, subjected to temporary focal cerebral ischemia by suture occlusion of the middle cerebral artery for 90 min, and sham controls were serially imaged at 4.7 Tesla. DT scans were collected repeatedly during the hyperacute (2 and 3.5 h), acute (1, 2, and 3 days), subacute (4, 7, and 14 days), and chronic (4, 6, and 8 weeks) phases. We measured the evolution of DT indices (mean diffusivity (MD), axial diffusivity (λ ║ ), radial diffusivity (λ ┴ ), and fractional anisotropy (FA)) in the cortex, subcortex, and corpus callosum of the ischemic hemisphere. In the hyperacute phase, MD, λ ║ , and λ ┴ reduced with no change in FA. From the acute to subacute phase, MD, λ ║ , and λ ┴ normalized and thereafter increased, whereas FA decreased in all the tissues. In the chronic phase, MD, λ ║ , and λ ┴ continued to rise, whereas FA normalized in the corpus callosum and subcortex, but remained low in the cortex. We described structural tissue changes in ischemic rat brain longitudinally utilizing DT analysis. DT indices reveal different individual patterns reflecting different facades and phases of tissue injury. The use of several DT indices may improve accuracy in estimating the age of the brain injury and in detecting ongoing pathological events.

The blood-brain barrier (BBB) is the principal regulator of blood-borne substance entry into the brain parenchyma. Therefore, BBB leakage, which leads to cerebral edema and influx of toxic substances, is common in pathological conditions such as cerebral ischemia, inflammation, trauma, and tumors. The leakage of BBB after ischemia-reperfusion injury has long been considered to be biphasic, although a considerable amount of discrepancies as for the timing of the second opening does exist among the studies. This led us to evaluate systematically and quantitatively the dynamics of BBB leakage in a rat model of 90-min ischemia-reperfusion, using gadolinium-enhanced (small molecule) magnetic resonance imaging and fluorescent dye Evans Blue (large molecule). BBB leakage was assessed at the following time points after reperfusion: 25 min, 2, 4, 6, 12, 18, 24, 36, 48, and 72 h, and 1, 2, 3, 4, and 5 weeks. We observed BBB leakage for both gadolinium and Evans Blue as early as 25 min after reperfusion. Thereafter, BBB remained open for up to 3 weeks for Evans Blue and up to 5 weeks for gadolinium. Our results show that BBB leakage after ischemia-reperfusion injury in the rat is continuous and long-lasting, without any closure up to several weeks. This is the first systematic and extensive study fully demonstrating BBB leakage dynamics following transient brain ischemia and the findings are of major clinical and experimental interest.

Two related ligands, glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), are expressed by Sertoli cells, but their cognate ligand-binding co-receptors, GDNF family receptor alpha1 and alpha2, are displayed by different germ cells suggesting different targets for the ligands. GDNF regulates cell fate decision of undifferentiated spermatogonia 'Science 287 (2000) 1489'. The role of NRTN was now approached by targeted overexpression in mouse testis. Between 3 and 5 weeks of age, transient degeneration of spermatogenic cells was observed in approximately 20% of all five transgenic lines generated. Spermatids and pachytene spermatocytes underwent segmental degeneration, if the rete testis was undilated. When it was dilated, the spermatids and spermatocytes were more generally depleted. After 5 weeks of age, spermatogenic defects were no more observed and the NRTN overexpressing mice were fertile. The data suggest that NRTN might regulate survival and differentiation of spermatocytes and spermatids, but the low penetrance indicates that either the transgene expression has not been high enough or NRTN is not as essential as GDNF for spermatogenesis.