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Advanced Neurology                                             Tetrapleura tetraptera protects the hippocampus



                                                               findings suggest that the administered doses of T. tetraptera
                                                               possess anticonvulsant activity, potentially reducing the
                                                               severity of PTZ-induced seizures, a result consistent
                                                               with a previous report.  Although the exact mechanism
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                                                               underlying  T. tetraptera’s anticonvulsant effect remains
                                                               to be elucidated, it is likely mediated through GABAergic
                                                               transmission. This hypothesis is supported by a prior study
                                                               indicating that alkaloids and flavonoids,  which are also
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                                                               constituents of T. tetraptera, enhance GABA transmission.
                                                                 Pentylenetetrazol administration resulted in mortality,
            Figure  7.  Glial fibrillary acidic protein (GFAP)-labeled cell count   with the PTZ group exhibiting a lower percentage of
            of  the  hippocampal  cornu  ammonis  3  region  of  the  experimental   quantal  protection,  suggesting  toxicity,  as  previously
            groups. A repeated measures analysis of variance and Tukey’s post-hoc   reported.  The groups pre-treated with sodium valproate,
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            tests were performed. Values are expressed as mean±standard error
            of mean. Notes:  Sample size per group: Control=3; TT=3; PTZ=3;   intermediate doses of  T. tetraptera, and intermediate
            PTZ+SV=3; PTZ+TT (low)=3; PTZ+TT (int)=3; PTZ+TT (high)=3.   doses of T. tetraptera demonstrated greater protection and
            ** and ***indicate significant differences from the control at p<0.01 and   lower mortality compared to the PTZ group, supporting
            p<0.001, respectively.  b,c,d,e,f Significantly different from TT, PTZ, PTZ+SV,   previous  findings.   Sodium  valproate, an  established
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            PTZ+TT (low),  PTZ+TT  (int),  and  PTZ+TT (high), respectively, at
            p<0.05.                                            antiepileptic drug (54), exhibited expected antiseizure
            Abbreviations: PTZ: pentylenetetrazol; SV: Sodium valproate;   activity, whereas  T. tetraptera’s effect may be attributed
            TT: Tetrapleura tetraptera.                        to its rich phytochemical constituents, which have
                                                               been shown to be safe in the present study. Notably, the
            over 5,000  mg/kg in mice, supporting the safety of the   high-dose  T. tetraptera-pretreatment  group  showed  no
            extract, as this concentration is typically the end-point   significant difference in  quantal  protection  or mortality
            of LD  determination.  These findings align with those   when compared to the PTZ group, suggesting that high
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                 50
            of a previous study,  which reported an LD  of over   doses of T. tetraptera may be unnecessary or potentially
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                                                  50
            10,000 mg/kg body weight in a mouse model.         harmful, either exacerbating or having no effect on PTZ
              Kindling is a recognized experimental model for   toxicity.
            human  epilepsy,  induced  through  sub-convulsive  doses   The spontaneous alternation behavior test is commonly
            of chemicals or electrical stimulation. 56,57  PTZ, a chemical   used to assess short-term memory and identify memory
            convulsant, exerts its effects by inhibiting GABA activity   impairments associated with various disease conditions. 11,48
            at the GABA  receptor, thus mimicking epilepsy.  In the   The present results revealed no significant difference
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                      A
            present study, PTZ administration resulted in increasing   (p>0.05) between the test and control groups, suggesting
            seizure scores and kindling, which progressively intensified   that the treatment regimens did not influence spontaneous
            with each administration. Increased seizure scores, as   alternation. This lack of effect may be attributed to the
            assessed using the Racine scale, denote the worsening   treatment’s inadequacy in influencing spatial brain
            seizure severity, consistent with previous reports. 45,57    functions. Given that spontaneous alternation is related to
            Sodium  valproate,  a standard  antiepileptic drug, failed   learning and memory,  this study found no impairment
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            to suppress seizures in this study, as the seizure scores in   in these functions. Chemical kindling models, including
            this group did not differ significantly from those in the   those using PTZ, have previously reported cognitive,
            PTZ group. This result contrasts with previous studies   learning, and  memory impairments.   The discrepancy
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            that reported antiseizure effects of sodium valproate at   between these findings and the present study could be
            doses of 200 and 300  mg/kg,  which were also used in   due to the animal model used. Furthermore, the current
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            the present study. While sodium valproate is known to   results contrast with another study in which PTZ kindling
            attenuate PTZ-induced seizures,  this contrasting result   resulted in learning and memory deficits in mice,
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            may be due to a spike in glycine levels, as sodium valproate   which may be attributed to the differences in behavioral
            also interferes with glycine synthesis, potentially leading to   paradigms tested.
            increased seizure frequency. 60                      Nissl substance, present in all neurons, is a rough
              T. tetraptera attenuated PTZ-induced kindling, with   endoplasmic  reticulum  component  essential  for
            significant reductions (p<0.05) in seizure scores observed   protein synthesis  and frequently disintegrates during
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            in the low-, intermediate-, and high-dose  T. tetraptera-  chromatolysis.  PTZ also affects this macromolecule.
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                                                                                                           9,56
            pretreated groups compared to the PTZ group.  These   In the current study, the CA3 hippocampal region of the
            Volume 4 Issue 1 (2025)                         88                               doi: 10.36922/an.6862
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