Evaluation of kynurenine pathway metabolism in Toxoplasma gondii-infected mice: Implications for schizophrenia

Toxoplasma gondii, an intracellular protozoan parasite, is a major cause of opportunistic infectious disease affecting the brain and has been linked to an increased incidence of schizophrenia. In murine hosts, infection with T. gondii stimulates tryptophan degradation along the kynurenine pathway (KP), which contains several neuroactive metabolites, including 3-hydroxykynurenine (3-HK), quinolinic acid (QUIN) and kynurenic acid (KYNA). As these endogenous compounds may provide a mechanistic connection between T. gondii and the pathophysiology of schizophrenia, we measured KP metabolites in both brain and periphery of T. gondii-treated C57BL/6 mice 8 and 28 days post-infection. Infected mice showed early decreases in the levels of tryptophan in brain and serum, but not in the liver. These reductions were associated with elevated levels of kynurenine, KYNA, 3-HK and QUIN in the brain. In quantitative terms, the most significant increases in these KP metabolites were observed in the brain at 28 days post-infection. Notably, the anti-parasitic drugs pyrimethamine and sulfadiazine, a standard treatment of toxoplasmosis, significantly reduced 3-HK and KYNA levels in the brain of infected mice when applied between 28 and 56 days post-infection. In summary, T. gondii infection, probably by activating microglia and astrocytes, enhances the production of KP metabolites in the brain. However, during the first two months after infection, the KP changes in these mice do not reliably duplicate abnormalities seen in the brain of individuals with schizophrenia

Successful Thrombectomy Improves Functional Outcome in Tandem Occlusions with a Large Ischemic Core

International audienceBackground: Emergent stenting in tandem occlusions and mechanical thrombectomy (MT) of acute ischemic stroke related to large vessel occlusion (LVO-AIS) with a large core are tested independently. We aim to assess the impact of reperfusion with MT in patients with LVO-AIS with a large core and a tandem occlusion and to compare the safety of reperfusion between large core with tandem and nontandem occlusions in current practice. Methods: We analyzed data of all consecutive patients included in the prospective Endovascular Treatment in Ischemic Stroke Registry in France between January 2015 and March 2023 who presented with a pretreatment ASPECTS (Alberta Stroke Program Early CT Score) of 0–5 and angiographically proven tandem occlusion. The primary end point was a favorable outcome defined by a modified Rankin Scale (mRS) score of 0–3 at 90 days. Results: Among 262 included patients with a tandem occlusion and ASPECTS 0–5, 203 patients (77.5%) had a successful reperfusion (modified Thrombolysis in Cerebral Infarction grade 2b-3). Reperfused patients had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR], 1.57 [1.22–2.03]; P < 0.001), higher rates of mRS score 0–3 (aOR, 7.03 [2.60–19.01]; P < 0.001) and mRS score 0–2 at 90 days (aOR, 3.85 [1.39–10.68]; P = 0.009) compared with nonreperfused. There was a trend between the occurrence of successful reperfusion and a decreased rate of symptomatic intracranial hemorrhage (aOR, 0.5 [0.22–1.13]; P = 0.096). Similar safety outcomes were observed after large core reperfusion in tandem and nontandem occlusions. Conclusions: Successful reperfusion was associated with a higher rate of favorable outcome in large core LVO-AIS with a tandem occlusion, with a safety profile similar to nontandem occlusion