Which Theory of Cerebrospinal Fluid Production and Absorption Do Neurosurgeons Teach to Medical Students? Survey from Medical Universities in Japan, 2022.

Several new studies have been conducted on cerebrospinal fluid (CSF) dynamics. Our educational guidelines, the Model Core Curriculum for Medical University, recommend access to the best current information. However, we do not know whether or when to introduce changes to this concept.We surveyed which theory of CSF dynamics taught to students by neurosurgeons. The old theory is the bulk flow theory, and the new theory explains that CSF is produced from the choroid plexus and capillaries; CSF then pulsates and drains into the venous and lymphatic systems through newly discovered pathways.Old and new theories were taught to 64.8% and 27.0% of students, respectively. The reason for teaching the old theory was to help them understand the pathogenesis of noncommunicating hydrocephalus (77.1%), whereas the reason for teaching the new theory was to teach the latest knowledge (40.0%). Physicians who wished to teach the new theory in the near future accounted for 47.3%, which was higher than those who would teach the new theory in 2022 (27.0%), and those who still wished to teach the old theory in the near future accounted for 43.2%.An education policy on CSF dynamics will be established when we interpret ventricular enlargement and its improvement by third ventriculostomy in noncommunicating hydrocephalus based on the new theory. The distributed answers in the survey shared that it is difficult to teach about CSF dynamics and provided an opportunity to discuss these issues.

Thrombolysis with rt-PA under Rivaroxaban Anticoagulation in a Hypertensive Rat Model of Intraluminal Middle Cerebral Artery Occlusion.

BACKGROUND: The aim of this study was to assess the risk and the threshold of hemorrhagic transformation (HT) after treatment with recombinant tissue plasminogen activator (rtPA) under the novel oral anticoagulant, rivaroxaban. METHODS: Fifty-three spontaneous hypertensive rats were used in this study. We performed transient middle cerebral artery occlusion for 270 minutes. Placebo, 10 mg/kg or 20 mg/kg rivaroxaban were administered via a stomach tube 180 minutes after induction of ischemia, and rtPA (10 mg/kg) was administered just before reperfusion. Ninety minutes after rivaroxaban administration we measured the rivaroxaban plasma concentration and prothrombin time (PT). HT volume was assessed by hemoglobin spectrophotometry. Additionally, infarct volume, IgG leakage volume, and neurological outcome were assessed. RESULTS: Rivaroxaban plasma concentration and PT increased in a dose dependent manner but were lower than human peak levels after a once-daily dose of 20 mg rivaroxaban. HT volume increased after treatment with 20 mg/kg rivaroxaban compared with placebo treated controls or those treated with 10 mg/kg rivaroxaban (26.5 ± 5.4, 26.8 ± 8.7, and 41.4 ± 12.6 µL in placebo, 10 mg/kg, and 20 mg/kg treated groups, respectively; P < .05). CONCLUSIONS: Our results suggest that even at therapeutic plasma concentrations, rivaroxaban may increase the risk of HT after thrombolysis in some conditions, such as hypertension and/or a prolonged ischemic period.

Mechanistic insight into neurotoxicity of tissue plasminogen activator-induced thrombolysis products in a rat intraluminal middle cerebral artery occlusion model.

Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) after ischemic stroke is effective. However, rtPA potentiates neuronal damage, and interactions between rtPA and thrombolysis products (TLP) have been reported to play a role in this. In the present study we investigated the mechanisms underlying rtPA- and TLP-induced neurotoxicity. Adult male Sprague-Dawley rats were subjected to 60-min intraluminal middle cerebral artery (MCA) occlusion, and then treated with rtPA (10 mg/kg), TLP, or saline. To evaluate the effects of a free radical scavenger, treatment with edaravone and TLP was evaluated. To investigate the role of red blood cells (RBCs), RBC-depleted TLP was used. Neurological deficit scores, infarct volume, and immuno-histochemical localization of oxidative end products for lipid and DNA (4-hydroxy-2-nonenal [4-HNE] and 8-hydroxy-deoxyguanosine [8-OHdG]) were evaluated. TLP increased the infarct volume, worsened the neurological deficits, and increased accumulations of 4-HNE and 8-OHdG. Edaravone treatment significantly reduced the lesion volume and improved the neurological score. Both infarct volume and accumulation of oxidative products were significantly suppressed when RBC-depleted TLP was used. In this mechanical model of MCA occlusion, rtPA-induced TLP, especially in the presence of RBCs, contributed to neuronal damage by accelerating free radical injury.