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Traumatic brain injury (TBI) is a public health problem characterized by a combination of immediate mechanical dysfunction of the brain tissue, and secondary damage. Based on the hypothesis that selected targets, such as Na + K + -ATPase are involved in the secondary damage after TBI and modulation of this enzyme activity by triterpene 3β, 6β, 16β-trihidroxilup-20 (29)-ene (TTHL) supports the ethnomedical applications of this plant, we decided to investigate whether previous TTHL treatment interrupts the progression of pathophysiology induced by TBI. Statistical analyses revealed that percussion fluid injury (FPI) increased Na + ,K + -ATPase activity in all isoform (α 1 and α 2/3 ) 15 min after neuronal injury. The FPI protocol inhibited Na + ,K + -ATPase activity total and α 1 isoform, increased [ 3 H]MK-801 binding but did not alter Dichloro-dihydro-fluorescein diacetate (DCFH-DA) oxidation, carbonylated proteins and free -SH groups 60 min after injury. The increase of immunoreactivity of protein PKC and state of phosphorylation of at Ser 16 of Na + ,K + -ATPase 60 min after FPI suggest the involvement of PKC on Na + ,K + -ATPase activity oscillations characterized by inhibition of total and α 1 isoform. Our experimental data also revealed that natural product rich in compounds such as triterpenes (TTHL; 30 mg/kg) attenuates [ 3 H]MK-801 binding increase, phosphorylation of the PKC and the Na + ,K + -ATPase alpha 1 subunit (Ser 16 ) induced by FPI. The previous TTHL treatment had not effect on motor disability but protected against spatial memory deficit, BDNF, TrKB expression decrease, protein carbonylation and hippocampal cell death 7 days after FPI. These data suggest that TTHL-induced reduction on initial damage limits the long-term secondary degeneration and supports neural repair or behavioral compensation after neuronal injury., (Copyright © 2019. Published by Elsevier B.V.)

Increasing evidence suggests that prostanoid receptors and their ligands may constitute valuable tools for development of new antiepileptic drugs. Thromboxane A 2 (TXA 2 ) is a major eicosanoid in cardiovascular homeostasis. TXA 2 exerts its action through the specific G protein-coupled TXA 2 receptor (TP). In addition to its crucial role in the cardiovascular system, TXA 2 and TPs play a role in the brain. Nevertheless, previously identified roles have been limited to cell protection of neurotoxicity, and the role of TPs on seizure activity was not investigated. Here we evaluated the effect of potent and selective TP agonist U-46619 on seizures induced by pentylenetetrazol (PTZ). Adult C57BL/6 mice received increasing doses of U-46619 (0, 30, 100 or 300 μg/kg). After 30 min we measured the latencies to myoclonic and generalized seizures induced by PTZ (60 mg/kg). We found that U-46619 increased the latency to PTZ-induced myoclonic jerks and tonic-clonic seizures. Moreover, U-46619 increased the immunocontent of phosphorylated Ser 657 at protein kinase C (PKC) alpha subunit, indicating PKC activation in the hippocampus and cerebral cortex. Levels of TPs were not altered by the agonist. Administration of a TP antagonist, SQ 29,548, did not alter seizures and did not blunt the anticonvulsant-like effect of the agonist. In summary, we showed that a potent and selective TP agonist, U-46619, increased seizure latency in mice. Activation of PKC signaling pathways may underlie the anticonvulsant-like effect. Further investigation is needed to understand the potential of TPs in seizure treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Malaria, parasitic disease considered a major health public problem, is caused by Plasmodium protozoan genus and transmitted by the bite of infected female Anopheles mosquito genus. Cerebral malaria (CM) is the most severe presentation of malaria, caused by P. falciparum and responsible for high mortality and enduring development of cognitive deficits which may persist even after cure and cessation of therapy. In the present study we evaluated selected behavioral, neurochemical and neuropathologic parameters after rescue from experimental cerebral malaria caused by P. berghei ANKA in C57BL/6 mice. Behavioral tests showed impaired nest building activity as well as increased marble burying, indicating that natural behavior of mice remains altered even after cure of infection. Regarding the neurochemical data, we found decreased α2/α3 Na + ,K + -ATPase activity and increased immunoreactivity of phosphorylated Na + ,K + -ATPase at Ser 943 in cerebral cortex after CM. In addition, [ 3 H]-Flunitrazepam binding assays revealed a decrease of benzodiazepine/GABA A receptor binding sites in infected animals. Moreover, in hippocampus, dot blot analysis revealed increased levels of protein carbonyls, suggesting occurrence of oxidative damage to proteins. Interestingly, no changes in the neuropathological markers Fluoro-Jade C, Timm staining or IBA-1 were detected. Altogether, present data indicate that behavioral and neurochemical alterations persist even after parasitemia clearance and CM recovery, which agrees with available clinical findings. Some of the molecular mechanisms reported in the present study may underlie the behavioral changes and increased seizure susceptibility that persist after recovery from CM and may help in the future development of therapeutic strategies for CM sequelae., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)