Cannabidiol Reduces Short- and Long-Term High Glutamate Release after Severe Traumatic Brain Injury and Improves Functional Recovery.

This study aimed to determine if orally administered cannabidiol (CBD) lessens the cortical over-release of glutamate induced by a severe traumatic brain injury (TBI) and facilitates functional recovery. The short-term experiment focused on identifying the optimal oral pretreatment of CBD. Male Wistar rats were pretreated with oral administration of CBD (50, 100, or 200 mg/kg) daily for 7 days. Then, extracellular glutamate concentration was estimated by cortical microdialysis before and immediately after a severe TBI. The long-term experiment focused on evaluating the effect of the optimal treatment of CBD (pre- vs. pre- and post-TBI) 30 days after trauma. Sensorimotor function, body weight, and mortality rate were evaluated. In the short term, TBI induced a high release of glutamate (738% ± 173%; p < 0.001 vs. basal). Oral pretreatment with CBD at all doses tested reduced glutamate concentration but with higher potency at when animals received 100 mg/kg (222 ± 33%, p < 0.01 vs. TBI), an effect associated with a lower mortality rate (22%, p < 0.001 vs. TBI). In the long-term experiment, the TBI group showed a high glutamate concentration (149% p < 0.01 vs. SHAM). In contrast, animals receiving the optimal treatment of CBD (pre- and pre/post-TBI) showed glutamate concentrations like the SHAM group (p > 0.05). This effect was associated with high sensorimotor function improvement. CBD pretreatment, but not pre-/post-treatment, induced a higher body weight gain (39% ± 2.7%, p < 0.01 vs. TBI) and lower mortality rate (22%, p < 0.01 vs. TBI). These results support that orally administered CBD reduces short- and long-term TBI-induced excitotoxicity and facilitated functional recovery. Indeed, pretreatment with CBD was sufficient to lessen the adverse sequelae of TBI.

Propylparaben Reduces the Long-Term Consequences in Hippocampus Induced by Traumatic Brain Injury in Rats: Its Implications as Therapeutic Strategy to Prevent Neurodegenerative Diseases.

BACKGROUND: Severe traumatic brain injury (TBI), an important risk factor for Alzheimer's disease, induces long-term hippocampal damage and hyperexcitability. On the other hand, studies support that propylparaben (PPB) induces hippocampal neuroprotection in neurodegenerative diseases. OBJECTIVE: Experiments were designed to evaluate the effects of subchronic treatment with PPB on TBI-induced changes in the hippocampus of rats. METHODS: Severe TBI was induced using the lateral fluid percussion model. Subsequently, rats received subchronic administration with PPB (178 mg/kg, TBI+PPB) or vehicle (TBI+PEG) daily for 5 days. The following changes were examined during the experimental procedure: sensorimotor dysfunction, changes in hippocampal excitability, as well as neuronal damage and volume. RESULTS: TBI+PEG group showed sensorimotor dysfunction (p < 0.001), hyperexcitability (64.2%, p < 0.001), and low neuronal preservation ipsi- and contralateral to the trauma. Magnetic resonance imaging (MRI) analysis revealed lower volume (17.2%; p < 0.01) and great damage to the ipsilateral hippocampus. TBI+PPB group showed sensorimotor dysfunction that was partially reversed 30 days after trauma. This group showed hippocampal excitability and neuronal preservation similar to the control group. However, MRI analysis revealed lower hippocampal volume (p < 0.05) when compared with the control group. CONCLUSION: The present study confirms that post-TBI subchronic administration with PPB reduces the long-term consequences of trauma in the hippocampus. Implications of PPB as a neuroprotective strategy to prevent the development of Alzheimer's disease as consequence of TBI are discussed.

Sodium Cromoglycate Decreases Sensorimotor Impairment and Hippocampal Alterations Induced by Severe Traumatic Brain Injury in Rats.

Severe traumatic brain injury (TBI) results in significant functional disturbances in the hippocampus. Studies support that sodium cromoglycate (CG) induces neuroprotective effects. This study focused on investigating the effects of post-TBI subchronic administration of CG on hippocampal hyperexcitability and damage as well as on sensorimotor impairment in rats. In contrast to the control group (Sham+SS group), animals undergoing severe TBI (TBI+SS group) showed sensorimotor dysfunction over the experimental post-TBI period (day 2, 55%, p < 0.001; day 23, 39.5%, p < 0.001; day 30, 38.6%, p < 0.01). On day 30 post-TBI, TBI+SS group showed neuronal hyperexcitability (63.3%, p < 0.01). The hippocampus ipsilateral to the injury showed volume reduction (14.4%, p < 0.001) with a volume of damage of 0.15 ± 0.09 mm3. These changes were associated with neuronal loss in the dentate gyrus (ipsilateral, 33%, p < 0.05); hilus (ipsilateral, 77%, p < 0.001; contralateral, 51%, p < 0.001); Cornu Ammonis (CA)1 (ipsilateral, 40%, p < 0.01), and CA3 (ipsilateral, 52%, p < 0.001; contralateral, 34%, p < 0.01). Animals receiving subchronic treatment with CG (50 mg/kg, s.c. daily for 10 days) after TBI (TBI+CG group) displayed a sensorimotor dysfunction less evident than that of the TBI+SS group (p < 0.001). Their hippocampal excitability was similar to that of the Sham+SS group (p = 0.21). The TBI+CG group presented hippocampal volume reduction (12.7%, p = 0.94) and damage (0.10 ± 0.03 mm3, p > 0.99) similar to the TBI+SS group. However, their hippocampal neuronal preservation was similar to that of the Sham+SS group. These results indicate that CG represents an appropriate and novel pharmacological strategy to reduce the long-term sensorimotor impairment and hippocampal damage and hyperexcitability that result as consequences of severe TBI.

Docosahexaenoic acid protection in a rotenone induced Parkinson's model: Prevention of tubulin and synaptophysin loss, but no association with mitochondrial function.

Rotenone, a classic mitochondrial complex I inhibitor, leads to dopaminergic neuronal death resulting in a Parkinson's-like-disease. Docosahexaenoic acid (DHA) has shown neuroprotective effects in other experimental models of Parkinson's disease, but its effect on the rotenone-induced parkinsonism is still unknown. We tested whether DHA in vivo exerts a neuroprotective effect on rotenone-induced parkinsonism and explored the mechanisms involved, including mitochondrial function and ultrastructure as well as the expression of tubulin and synaptophysin. We pretreated eighty male Wistar rats with DHA (35 mg/kg/day) for seven days and then administered rotenone for eight days. We then measured rearing behavior, number of dopaminergic neurons, tyrosine hydroxylase content, tubulin and synaptophysin expression, mitochondrial complex I, respiratory control ratio, mitochondrial transmembrane potential, ATP production activity and mitochondrial ultrastructure. We found that in vivo DHA supply exerted a neuroprotective effect, evidenced by decreased dopaminergic neuron cell death. Although we detected rotenone induced mitochondrial ultrastructure alterations, these were not associated with mitochondrial dysfunction. Rotenone had no effect on mitochondrial complex I, respiratory control ratio, mitochondrial transmembrane potential or ATP production activity. DHA also prevented a rotenone-induced decrease in tubulin and synaptophysin expression. Our results support the neuroprotective effect of DHA on rotenone-induced parkinsonism, and a possible effect on early stage Parkinson's disease. This protective effect is not associated with mitochondrial function improvement, but rather with preventing loss of tubulin and synaptophysin, proteins relevant to synaptic transmission.

Sodium cromoglycate reduces short- and long-term consequences of status epilepticus in rats.

Several studies indicate that sodium cromoglycate (CG) induces neuroprotective effects in acute neurological conditions. The present study focused on investigating if the use of CG in rats during the post-status epilepticus (post-SE) period reduces the acute and long-term consequences of seizure activity. Our results revealed that animals that received a single dose of CG (50 mg/kg s.c.: subcutaneously) during the post-SE period showed a lower number of neurons in the process of dying in the dentate gyrus, hilus, cornu ammonis 1 (CA1), and CA3 of the dorsal hippocampus than the rats that received the vehicle. However, this effect was not evident in layers V-VI of the sensorimotor cortex or the lateral-posterior thalamic nucleus. A second experiment showed that animals that received CG subchronically (50 mg/kg s.c. every 12 h for 5 days followed by 24 mg/kg/day s.c. for 14 days using osmotic minipumps) after SE presented fewer generalized convulsive seizures and less neuronal damage in the lateral-posterior thalamic nucleus but not in the hippocampus or cortex. Our data indicate that CG can be used as a therapeutic strategy to reduce short- and long-term neuronal damage in the hippocampus and thalamus, respectively. The data also indicate that CG can reduce the expression of generalized convulsive spontaneous seizures when it is given during the latent period of epileptogenesis.

Propylparaben applied after pilocarpine-induced status epilepticus modifies hippocampal excitability and glutamate release in rats.

Propylparaben (PPB) induces cardioprotection after ischemia-reperfusion injury by inhibiting voltage-dependent Na+ channels. The present study focuses on investigating whether the i.p. application of 178mg/kg PPB after pilocarpine-induced status epilepticus (SE) reduces the acute and long-term consequences of seizure activity. Initially, we investigated the effects of a single administration of PPB after SE. Our results revealed that compared to rats receiving diazepam (DZP) plus vehicle after 2h of SE, animals receiving a single dose of PPB 1h after DZP injection presented 126% (p<0.001) lower extracellular levels of glutamate in the hippocampus. This effect was associated with an increased potency of low-frequency oscillations (0.1-13Hz bands, p<0.001), a reduced potency of 30-250Hz bands (p<0.001) and less neuronal damage in the hippocampus. The second experiment examined whether the subchronic administration of PPB during the post-SE period is able to prevent the long-term consequences of seizure activity. In comparison to animals that were treated subchronically with vehicle after SE, rats administered with PPB for 5 days presented lower hippocampal excitability and interictal glutamate release, astrogliosis, and neuroprotection in the dentate gyrus. Our data indicate that PPB, when applied after SE, can be used as a therapeutic strategy to reduce the consequences of seizure activity.

The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p < 0.001) and neuronal damage in dentate gyrus, CA1 and CA3. In contrast to SS-SE group, rats from the CG-SE group showed increased latency to the establishment of the status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment.

Role of histaminergic system in blood-brain barrier dysfunction associated with neurological disorders.

Blood-brain barrier (BBB) disruption has been associated with several acute and chronic brain disorders such as Alzheimer's disease, Parkinson's disease and epilepsy. This represents a critical situation because damaged integrity of the BBB is related to the influx of immune mediators, plasma proteins and other outside elements from blood to the central nervous system (CNS) that may trigger a cascade of events that leads to neuroinflammation. In this review, evidence that mast cells and the release of factors such as histamine play an important role in the neuroinflammatory process associated with brain disorders such as Alzheimer's disease, Parkinson's disease and epilepsy is presented.

Estudio de la flora alergénica en el Valle de México. Relación con la sensibilización alimenticia de origen vegetal (primera parte) / Allergenic flora in the Valle de Mexico. Relation with food sensitivity of vegetable origen (Part 1)

Se realizo un analisis descriptivo de las plantas consideradas capaces de producir reaccion alergica por los granos de polen. Se trabajo con 106 especimenes de 30 familias y 79 generos, solo 57 especies contribuyeron a la coleccion con preparaciones fijas de polen acetolizado. Asimismo, se realizaron descripciones morfologicas del grano de polen. Se revisaron historias clinicas, seleccionandose a los pacientes que dieron reaccion positiva a algun polosn (1 101 pacientes) y reaccion positiva a algun alimento. Esto se corroboro con pruebas de ingestion alimentaria de origen vegetal. Las gramineas, leguminosas rosaceas y solanaceas fueron el grupo mas importante de alimentos de origen vegetal que dieron reaccion positiva por ingestion alimentaria y 37.52% a reaccion cutanea.