Background and Purpose-Early reperfusion using tissue-type plasminogen activator is the only therapeutic agent to treat focal cerebral ischemia with proven efficacy in patients. Nevertheless, novel insights into the pathophysiology of neurons, glial cells, and the fate of the endothelium after stroke call for the use of new strategies to improve stroke treatment alone or in combination with tissue-type plasminogen activator-induced thrombolysis. Unfortunately, despite the plethora of drugs that display clear beneficial effects in animal models of experimental ischemia, their subsequent use in clinical trials has proven disappointing. As such, one is forced to consider that new animal models of focal cerebral ischemia may be required before clinical evaluation of a new molecule. Methods-In situ microinjection of purified murine thrombin was used to trigger a local clot formation in anesthetized mice. Cerebral blood velocity was measured continuously throughout the duration of the study. The efficiency of recombinant tissue-type plasminogen activator to induce thrombolysis and its subsequent effect on infarct volume were then measured. Results-In situ thrombin injection leads to a reproducible clot formation and cortical brain injury. Recombinant tissue-type plasminogen activator-induced thrombolysis reduced infarct volume by 36.8% when compared with untreated control mice. Conclusions-We describe an original and reproducible mouse model of in situ clot formation and reperfusion, which could be used to investigate new therapeutic strategies to improve stroke treatment.

We used functional magnetic resonance imaging to determine the cerebral structures required during the recollection of episodic autobiographical memories according to 5 time periods covering the whole lifespan to test the 2 concurring models of memory consolidation, which propose either a temporary (standard model) or a permanent (multiple-trace model) role of the hippocampus in episodic memory retrieval. The experimental paradigm was specially designed to engage subjects (67.17 +/- 5.22 years old) in the retrieval of episodic autobiographical memories, whatever the time period, from personally relevant cues selected by questioning a family member. Moreover, the nature of the memories was checked at debriefing by means of behavioral measures to control the degree of episodicity. Behavioral data showed that recollected memories were characterized by specificity and details whatever their remoteness. Main neuroimaging data (Statistical Parametric Mapping 99) revealed the activation of a network including the left superior frontal gyri, bilateral precuneus/posterior cingulate and lingual gyri, left angular gyrus, and left hippocampus, although the subtraction analyses detected subtle differences between certain time periods. Small volume correction centered on the hippocampus detected left hippocampal activation for all time periods and additional right hippocampal activation for the intermediate periods. Further confirmation was provided by using a 3-way analysis of variance on blood oxygen level-dependent values, which revealed hippocampal activation whatever the time interval. The present data challenge the standard model of memory consolidation and support the multiple-trace model, instead. The comparison with previous literature stresses the idea that a bilateral involvement of the hippocampus characterizes rich episodic autobiographical memory recollection.