Early treatment with dapsone after spinal cord injury in rats decreases the inflammatory response and promotes long-term functional recovery.

Failure of therapeutic strategies for the management and recovery from traumatic spinal cord injury (SCI) is a serious concern. Dapsone (DDS) has been reported as a neuroprotective drug after SCI, although the phase after SC damage (acute or chronic) of its major impact on functional recovery has yet to be defined. Here, we evaluated DDS acute-phase anti-inflammatory effects and their impact on early functional recovery, one week after moderate SCI, and late functional recovery, 7 weeks thereafter. Female Wistar rats were randomly assigned to each of five experimental groups: sham group; four groups of rats with SCI, treated with DDS (0, 12.5, 25.0, and 37.5 mg/kg ip), starting 3 h after injury. Plasma levels of GRO/KC, and the number of neutrophils and macrophages in cell suspensions from tissue taken at the site of injury were measured as inflammation biomarkers. Hindlimb motor function of injured rats given DDS 12.5 and 25.0 mg/kg daily for 8 weeks was evaluated on the BBB open-field ordinal scale. Six hours after injury all DDS doses decreased GRO/KC plasma levels; 24 h after injury, neutrophil numbers decreased with DDS doses of 25.0 and 37.5 mg/kg; macrophage numbers decreased only at the 37.5 mg/kg dose. In the acute phase, functional recovery was dose-dependent. Final recovery scores were 57.5 and 106.2% above the DDS-vehicle treated control group, respectively. In conclusion, the acute phase dose-dependent anti-inflammatory effects of DDS impacted early motor function recovery affecting final recovery at the end of the study.

Characterization of the anticonvulsant effect of dapsone on metabolic activity assessed by [18F]FDG -PET after kainic acid-induced status epilepticus in rats.

BACKGROUND: Development of effective drugs for epilepsy are needed, as nearly 30 % of epileptic patients, are resistant to current treatments. This study is aimed to characterize the anticonvulsant effect of dapsone (DDS), in the kainic acid (KA)-induced Status Epilepticus (SE) by recording the brain metabolic activity with an [18F]FDG-PET analysis. METHODS: Wistar rats received KA (10 mg/kg, i.p., single dose) to produce sustained seizures. [18F]FDG-PET and electroencephalographic (EEG) studies were then performed. DDS or vehicle were administered 30 min before KA. [18F]FDG uptake and EEG were evaluated at baseline, 2 and 25 h after KA injection. Likewise, caspase-8, 3 hippocampal activities and Fluoro-Jade B neuronal degeneration and Hematoxylin-eosin staining were measured 25 h after KA. RESULTS: PET data evaluated at 2 h showed hyper-uptake of [18F]FDG in the control group, which was decreased by DDS. At 25 h, hypo-uptake was observed in the control group and higher values due to DDS effect. EEG spectral power was increased 2 h after KA administration in the control group during the generalized tonic-clonic seizures, which was reversed by DDS, correlated with [18F]FDG-PET uptake changes. The values of caspases-8 activity decreased 48 and 43 % vs control group in the groups treated with DDS (12.5 y 25 mg/kg respectively), likewise; caspase-3 activity diminished by 57 and 53 %. Fewer degenerated neurons were observed due to DDS treatments. CONCLUSIONS: This study pinpoints the anticonvulsant therapeutic potential of DDS. Given its safety and effectiveness, DDS may be a viable alternative for patients with drug-resistant epilepsy.

The acute systemic toxicity of thallium in rats produces oxidative stress: attenuation by metallothionein and Prussian blue.

Thallium (TI) is one of the most toxic heavy metals. Human exposure to Tl occurs through contaminated drinking water and from there to food, a threat to health. Recently, environmental contamination by Tl has been reported in several countries, urging the need for studies to determine the impact of endogenous and exogenous mechanisms preventing thallium toxicity. The cytoprotective effect of metallothionein (MT), a protein with high capacity to chelate metals, at two doses (100 and 600 µg/rat), was tested. Prussian blue (PB) (50 mg/kg) was administered alone or in combination with MT. A dose of Tl (16mg/kg) was injected i.p. to Wistar rats. Antidotes were administered twice daily, starting 24h after Tl injection, for 4 days. Tl concentrations diminished in most organs (p < 0.05) by effect of PB, alone or in combination with MT, whereas MT alone decreased Tl concentrations in testis, spleen, lung and liver. Likewise, brain thallium also diminished (p < 0.05) by effect of PB and MT alone or in combination in most of the regions analyzed (p < 0.05). The greatest diminution of Tl was achieved when the antidotes were combined. Plasma markers of renal damage increased after Tl administration, while PB and MT, either alone or in combination, prevented the raise of those markers. Only MT increased the levels of reduced glutathione (GSH) in the kidney. Finally, increased Nrf2 was observed in liver and kidney, after treatment with MT alone or in combination with PB. Results showed that MT alone or in combination with PB is cytoprotective after thallium exposure.

Characterization of metabolic activity induced by kainic acid in adult rat whole brain at the early stage: A 18FDG-PET study.

OBJECTIVE: Brain metabolic processes are not fully characterized in the kainic acid (KA)-induced Status Epilepticus (KASE). Thus, we evaluated the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as an experimental strategy to evaluate in vivo, in a non-invasive way, the glucose consumption in several brain regions, in a semi-quantitative study to compare and to correlate with data from electroencephalography and histology studies. METHODS: Sixteen male Wistar rats underwent FDG-PET scans at basal state and after KA injection. FDG-PET images were normalized to an MRI-based atlas and segmented to locate regions. Standardized uptake values (SUV) were obtained at several time points. EEGs and cell viability by histological analysis, were also evaluated. RESULTS: FDG-PET data showed changes in regions such as: amygdala, hippocampus, accumbens, entorhinal cortex, motor cortex and hypothalamus. Remarkably, hippocampal hypermetabolism was found (mean SUV = 2.66 ± 0.057) 2 h after KA administration, while hypometabolism at 24 h (mean SUV = 1.83 ± 0.056) vs basal values (mean SUV = 2.19 ± 0.057). EEG showed increased spectral power values 2 h post-KA administration. Hippocampal viable-cell counting 24 h after KA was decreased, while Fluoro-Jade B-positive cells were increased, as compared to control rats, coinciding with the hypometabolism detected in the same region by semi-quantitative FDG-PET at 24 h after KASE. CONCLUSIONS: PET is suitable to measure metabolic brain changes in the rat model of status epilepticus induced by KA (KASE) at the first 24 h, compared to that of EEG; PET data may also be sensitive to cell viability.

Characterization of the antiapoptotic effect of copper sulfate on striatal and midbrain damage induced by MPP+ in rats.

1-Methyl-4-phenylpyridinium ion (MPP+)-induced neurotoxicity produces cellular damage resembling that encountered in Parkinson's disease. The mechanisms of cellular death after MPP+ include the participation of oxidative stress in the loss of dopaminergic neurons. Among the mechanisms of defense against oxidative stress, several copper-dependent proteins have been implicated: Cu/Zn-SOD, ceruloplasmin, and metallothionein. Another important mechanism of damage, is MPP + interference with mitochondrial respiration. Both, oxidative stress and inhibition of mitochondrial respiration may trigger apoptosis in the neurons after MPP+. The aim of the present study was to characterize the time-course of apoptosis induced by MPP+ to determine if copper sulfate pretreatment is able to prevent the activation of caspases and decreased the neuronal apoptosis. MPP+ was microinjected into rat striatum using a stereotactic frame. The results showed increased activities of caspases 8, 9 and 3, between 72-120 hours after administration of MPP+, both in striatum and midbrain. After this study, we tested the effect of CuSO4 on MPP+ neurotoxicity, showing a diminution of the apoptotic damage induced by MPP+, decreased levels of enzymatic activity of caspases: 8 (-34 and -25 %), 9 (-25 and -42 %) and 3 (-40 and -29 %) in striatum and midbrain, respectively. Finally, we performed an immunohistochemical analysis, evidencing a decreased number of apoptotic cells in the groups pretreated with copper sulfate pretreatment compared to the control group. With these findings, it is concluded that pretreatment with copper sulfate may be a good alternative to prevent MPP+-induced apoptosis.

Immunohistochemical Study of Antioxidant Enzymes Regulated by Nrf2 in the Models of Epileptic Seizures (KA and PTZ).

Epilepsy is a neurological disorder characterized by recurrent spontaneous seizures due to an imbalance between cerebral excitability and inhibition, with a tendency towards uncontrolled excitability. Epilepsy has been associated with oxidative and nitrosative stress due to prolonged neuronal hyperexcitation and loss neurons during seizures. The experimental animal models report level of ATP diminished and increase in lipid peroxidation, catalase, and glutathione altered activity in the brain. We studied the immunohistochemical expression and localization of antioxidant enzymes GPx, SOD, and CAT in the rat brains treated with KA and PTZ. A significant decrease was observed in the number of immunoreactive cells to GPx, without significant changes for SOD and CAT in KA-treated rats, and decrease in the number of immunoreactive cells to SOD, without significant changes for GPx and only CAT in PTZ-treated rats. Evident immunoreactivity of GPx, SOD, and CAT was observed mainly in astrocytes and neurons of the hippocampal brain region in rats exposed at KA; similar results were observed in rats treated with PTZ at the first hours. These results provide evidence supporting the role of activation of the Nrf2 antioxidant system pathway against oxidative stress effects in the experimental models of epileptic seizures.

Efficacy of dapsone administered alone or in combination with diazepam to inhibit status epilepticus in rats.

Status epilepticus (SE) is a serious medical condition, as it may trigger epileptogenesis. SE produces continuous generalized seizures resulting in irreversible brain damage. Therefore, the use of neuroprotective agents to prevent cell damage, may reduce the impact of SE. The use of diazepam (DZP), has shown limited neuroprotective effect in SE patients. According to previous reports, dapsone (DDS) is able to reduce both cell damage and seizures, when administered 30 min before the onset of seizures. This study is aimed to evaluate the ability of DDS, alone or in combination with DZP starting their administration once the SE is onset to evaluate the control of seizures in rats. Results showed a reduced convulsive electrical activity after 30 min, 1 and 2 h after SE induced by kainic acid (KA) administration, in the animals treated with DZP alone or in combination with DDS. At 24 h, we observed electrical activity similar to baseline in all groups receiving treatment. The animals treated with DDS and DZP alone or in combination showed an increase in the number of viable pyramidal cells but only the combination showed a lower number of damaged pyramidal neurons of hippocampal CA3. In conclusion, DDS plus DZP was able to control SE and to prevent SE-induced damage, when administered in combination with DZP. As DDS is already in use for patients with leprosy, that combination may be a safe, good option for human cases of SE.

Metallothionein-I + II Reduces Oxidative Damage and Apoptosis after Traumatic Spinal Cord Injury in Rats.

After spinal cord injury (SCI), some self-destructive mechanisms start leading to irreversible neurological deficits. It is known that oxidative stress and apoptosis play a major role in increasing damage after SCI. Metallothioneins I and II (MT) are endogenous peptides with known antioxidant, neuroprotective capacities. Taking advantage of those capacities, we administered exogenous MT to rats after SCI in order to evaluate the protective effects of MT on the production of reactive oxygen species (ROS) and lipid peroxidation (LP), as markers of oxidative stress. The activities of caspases-9 and -3 and the number of annexin V and TUNEL-positive cells in the spinal cord tissue were also measured as markers of apoptosis. Rats were subjected to either sham surgery or SCI and received vehicle or two doses of MT (10 µg per rat) at 2 and 8 h after surgical procedure. The results showed a significant increase in levels of MT protein by effect of SCI and SCI plus treatment at 12 h, while at 24 h an increase of MT was observed only in the injury plus treatment group (p < 0.05). ROS production was decreased by effect of MT in lesioned tissue; likewise, we observed diminished LP levels by MT effect both in the sham group and in the group with SCI. Also, the results showed an increase in the activity of caspase-9 due to SCI, without changes by effect of MT, as compared to the sham group. Caspase-3 activity was increased by SCI, and again, MT treatment reduced this effect only at 24 h after injury. Finally, the results of the number of cells positive to annexin V and TUNEL showed a reduction due to MT treatment both at 24 and 72 h after the injury. With the findings of this work, we conclude that exogenously administered MT has antioxidant and antiapoptotic effects after SCI.

Metallothionein in Brain Disorders.

Metallothioneins are a family of proteins which are able to bind metals intracellularly, so their main function is to regulate the cellular metabolism of essential metals. There are 4 major isoforms of MTs (I-IV), three of which have been localized in the central nervous system. MT-I and MT-II have been localized in the spinal cord and brain, mainly in astrocytes, whereas MT-III has been found mainly in neurons. MT-I and MT-II have been considered polyvalent proteins whose main function is to maintain cellular homeostasis of essential metals such as zinc and copper, but other functions have also been considered: detoxification of heavy metals, regulation of gene expression, processes of inflammation, and protection against free radicals generated by oxidative stress. On the other hand, the MT-III has been related in events of pathogenesis of neurodegenerative diseases such as Parkinson and Alzheimer. Likewise, the participation of MTs in other neurological disorders has also been reported. This review shows recent evidence about the role of MT in the central nervous system and its possible role in neurodegenerative diseases as well as in brain disorders.

ß-Estradiol-3-benzoate confers neuroprotection in Parkinson MPP+ rat model through inhibition of lipid peroxidation.

Estradiol (E2), in addition to its known hormone function, is a neuroactive steroid that has shown neuroprotective profile in several models of neurological diseases. The present study explores the antioxidant effect of ß-estradiol-3-benzoate (EB) on the neurotoxicity elicited by MPP+ in rat striatum. Male Wistar rats, that were gonadectomized 30days prior to EB, were given 100µgEB per rat every 48h for 11days and animals were infused with MPP+ via intrastriatal at day six after beginning EB treatment. EB treatment completely prevented the fall in dopamine caused by MPP+, such result was related with decreased lipid peroxidation, a marker of oxidative stress; diminished number of ipsilateral-to-lesion turns and increased signal of the dopamine-synthesizing enzyme Tyrosin Hydroxylase in substantia nigra. The protection elicited by EB was not related to Mn or Cu-Zn superoxide dismutase enzymatic activities or glutathione modulation since none of these parameters were influenced by EB at the times assayed. Whereas, increased expression of PON2 as a result of EB treatment was observed, this phenomenon could be one of the mechanism by which the steroid conferred protection to dopaminergic cells against MPP+ injury.

Immunohistochemical study of Metallothionein in patients with temporal lobe epilepsy.

Epilepsy is characterized by spontaneous recurrent seizures and temporal lobe epilepsy (TLE) is the most common serious neurological example of acquired and frequent epilepsy. Oxidative stress is recognized as playing a contributing role in several neurological disorders, and most recently have been implicated in acquired epilepsies. The MTs occur in several brain regions and may serve as neuroprotective proteins against reactive oxygen species causing oxidative damage and stress. The main aim of this work was to describe the immunohistochemical localization of MT in the specimens derived from the patients affected by TLE. Histopathological examination showed NeuN, GFAP and MT immunopositive cells that were analyzed for determinate in hippocampal and parietal cortex samples. An increase in the reactive gliosis associated with increased MT expression was observed in patients with TLE.

Dapsone improves functional deficit and diminishes brain damage evaluated by 3-Tesla magnetic resonance image after transient cerebral ischemia and reperfusion in rats.

Stroke is a frequent cause of death and the first of disability in the world population. We have shown that dapsone acts as an antioxidant, antiinflammatory and antiapoptotic agent after brain Ischemia reperfusion (I/R) in rats; however, its therapeutic efficacy, measured by imaging has not been characterized. In this context, the aim of this study was to evaluate the neuroprotective effect of dapsone by magnetic resonance imaging (MRI) and to correlate imaging markers with motor function and oxidative stress after transient cerebral ischemia and reperfusion (I/R). We used male rats throughout the experiment. Functional deficit after I/R was assessed by using Longa scale. The area of brain tissue damage was measured by histology. The nuclear factor erythroid 2-related factor 2 (Nrf-2) and the amount of reactive oxygen species (ROS) were measured as biomarkers of oxidative stress. Finally, difussion tensor MRI was employed to measure the fractional anisotropy (FA), as a MRI marker of the pathophysiologic brain status. Results showed a better functional recovery and less damaged tissue in animals treated with dapsone vs control group. The values of FA were higher in animals receiving treatment, indicating a better preservation of brain structure. At early stages of the damage, dapsone was able to reduce both oxidative markers (Nrf-2 and ROS). Our findings provide new evidence for the efficacy of dapsone when administered during the acute phase after I/R and that quantitative sequences of MRI are useful for characterizing its potential therapeutic benefits after stroke.

Metallothionein expression in the rat brain following KA and PTZ treatment.

Epilepsy is a neurological disorder that has been associated with oxidative stress therefore epilepsy models have been develop such as kainic acid and pentylenetetrazol are usually used to understanding of the molecular mechanisms of this disease. We examined the metallothionein expression in rat brains of treated with kainic acid and pentylenetetrazol. Increase in metallothionein and nitrotirosyne immunoreactivity of both seizures epilepsy models was observed. Moreover, we show a significant increase on levels of MT expression. These results suggest that the increase of metallothionein expression is related with kainic acid and pentylenetetrazol treatments as response to damage mediated by oxidative stress.

Immunohistochemical Study of Nrf2-Antioxidant Response Element as Indicator of Oxidative Stress Induced by Cadmium in Developing Rats.

In developing animals, Cadmium (Cd) induces toxicity to many organs including brain. Reactive oxygen species (ROS) are often implicated in Cd-inducedtoxicity and it has been clearly demonstrated that oxidative stress interferes with the expression of genes as well as transcriptional factors such as Nrf2-dependent Antioxidant Response Element (Nrf2-ARE). Cd-generated oxidative stress and elevated Nrf2 activity have been reported in vitro and in situ cells. In this study we evaluated the morphological changes and the expression pattern of Nrf2 and correlated them with the Cd concentrations in different ages of developing rats in heart, lung, kidney, liver, and brain. The Cd content in different organs of rats treated with the metal was increased in all ages assayed. Comparatively, lower Cd brain levels were found in rats intoxicated at the age of 12 days, then pups treated at 5, 10, or 15 days old, at the same metal dose. No evident changes, as a consequence of cadmium exposure, were evident in the morphological analysis in any of the ages assayed. However, Nrf2-ARE immunoreactivity was observed in 15-day-old rats exposed to Cd. Our results support that fully developed blood-brain barrier is an important protector against Cd entrance to brain and that Nrf2 increased expression is a part of protective mechanism against cadmium-induced toxicity.

Anti-Apoptotic Effects of Dapsone After Spinal Cord Injury in Rats.

Spinal cord injury (SCI) is a condition producing irreversible damage to the neurological function. Among the leading mechanisms associated to cell death after SCI, excitotoxicity, oxidative stress, inflammatory response and apoptosis are considered potential targets to prevent tissue damage. We recently reported that dapsone an anti-inflammatory drug, decreases the activity of myeloperoxidase, lipid peroxidation, improve neurological function and increase the amount of spared tissue after SCI in rats. In this study, we characterized the anti-apoptotic effect of dapsone administered at 12.5 mg/kg/24 h dose, starting at 3 and 5 h after SCI. We monitored the activity of caspases-8, 9, and 3 and quantitated Annexin V and TUNEL positive cells in the core of the lesion. Results showed increased activities of caspase-8, 9 and 3 at 72 h by SCI to reach increments of 69, 143 and 293 %, respectively, as compared to sham group. Meanwhile, dapsone, administered at 3 and 5 after SCI, reduced caspase-8 activity by 36 and 44 % respectively, whereas the activity of caspase-9 was diminished by 37 %. Likewise, the activity of caspase-3 showed a decrease of 38 %. Finally, both Annexin V and TUNEL-positive cells were significantly reduced by DDS as compared to untreated SCI animals. Results showed that dapsone exerted anti-apoptotic effect after SCI.

Metallothionein-II inhibits lipid peroxidation and improves functional recovery after transient brain ischemia and reperfusion in rats.

After transient cerebral ischemia and reperfusion (I/R), damaging mechanisms, such as excitotoxicity and oxidative stress, lead to irreversible neurological deficits. The induction of metallothionein-II (MT-II) protein is an endogenous mechanism after I/R. Our aim was to evaluate the neuroprotective effect of MT-II after I/R in rats. Male Wistar rats were transiently occluded at the middle cerebral artery for 2 h, followed by reperfusion. Rats received either MT (10 µg per rat i.p.) or vehicle after ischemia. Lipid peroxidation (LP) was measured 22 h after reperfusion in frontal cortex and hippocampus; also, neurological deficit was evaluated after ischemia, using the Longa scoring scale. Infarction area was analyzed 72 hours after ischemia. Results showed increased LP in frontal cortex (30.7%) and hippocampus (26.4%), as compared to control group; this effect was fully reversed by MT treatment. Likewise, we also observed a diminished neurological deficit assessed by the Longa scale in those animals treated with MT compared to control group values. The MT-treated group showed a significant (P < 0.05) reduction of 39.9% in the infarction area, only at the level of hippocampus, as compared to control group. Results suggest that MT-II may be a novel neuroprotective treatment to prevent ischemia injury.

Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy.

Epilepsy is considered one of the most common neurological disorders worldwide. Oxidative stress produced by free radicals may play a role in the initiation and progression of epilepsy; the changes in the mitochondrial and the oxidative stress state can lead mechanism associated with neuronal death pathway. Bioenergetics state failure and impaired mitochondrial function include excessive free radical production with impaired synthesis of antioxidants. This review summarizes evidence that suggest what is the role of oxidative stress on induction of apoptosis in experimental models of epilepsy.

Activation of heme oxygenase recovers motor function after spinal cord injury in rats.

Characterization of auto-destructive mechanisms, leading to cell death after spinal cord injury (SCI) is important to prevent further damage to tissue. Heme oxygenase (HO) catalyzes the oxidation of heme to biliverdin and carbon monoxide (CO), as a response to cell damage. Products of HO action have biological effects, as antioxidant biliverdin. We evaluated the changes of HO activity after injury, and the effect of pharmacological treatments with hemin (an inducer) and (Sn)-protoporphyrin (an inhibitor, Sn-PPIX) of HO, upon motor recovery after SCI. Female Wistar rats were submitted to SCI by trauma and sacrificed at several times (2, 4, 8, 12 and 24h) after injury to evaluate HO activity. Additional groups of rats were treated with either hemin or Sn-PPIX, to evaluate motor recovery, spared spinal cord tissue and HO activity. Results showed that HO control activity was increased by effect of SCI, at all times evaluated, as compared to sham group values. Twenty-four hours after injury, HO activity was increased 7.2-fold by hemin treatment, as compared to SCI plus vehicle group values. In addition, animals treated with hemin 2 and 8h after SCI, showed a better motor recovery and higher spared cord tissue, as compared to control group values. Our findings indicate that activation of HO is a beneficial mechanism when attained during the acute phase after SCI.

Antioxidant, anticonvulsive and neuroprotective effects of dapsone and phenobarbital against kainic acid-induced damage in rats.

Excitotoxicity due to glutamate receptors (GluRs) overactivation is a leading mechanism of oxidative damage and neuronal death in various diseases. We have shown that dapsone (DDS) was able to reduce both neurotoxicity and seizures associated to the administration of kainic acid (KA), an agonist acting on AMPA/KA receptors (GluK1-GluK5). Recently, it has been shown that phenobarbital (PB) is also able to reduce epileptic activity evoked by that receptor. In the present study, we tested the antioxidative, anticonvulsive and neuroprotective effects of DDS and PB administered alone or in combination upon KA toxicity to rats. Results showed that KA increased lipid peroxidation and diminished reduced glutathione (GSH), 24 h after KA administration and both drugs in combination or individually inhibited these events. Likewise, KA promotes mortality and this event was antagonized by effect of both treatments. Additionally, the behavioral evaluation showed that DDS and PB administered alone or in combination decreased the number of limbic seizures and reduced the percentage of animals showing tonic-clonic seizures versus the control group, which was administered only with KA. Finally, our study demonstrated that all of the treatments prevented the neuronal death of the pyramidal cell layer of hippocampal CA-3. In conclusion, the treatment with DDS and PB administrated alone or in combination exerted antioxidant, anticonvulsive and neuroprotective effects against the neurotoxicity induced by KA in rats, but their effects were not additive. Thus, it may be good options of treatment in diseases such as epilepsy and status epilepicus, administered separately.

Plasma polypyrrole implants recover motor function in rats after spinal cord transection.

We studied the use of three biocompatible materials obtained by plasma polymerization of pyrrole (PPy), pyrrole doped with iodine (PPy/I) and a copolymer formed with pyrrole and polyethylene glycol (PPy/PEG), implanted, separately, after a complete spinal cord transection in rats. Motor function assessed with the BBB scale and somatosensory evoked potentials (SEPs) in the implanted rats were studied. Results showed that the highest motor recovery was obtained in rats with PPy/I implants. They also showed a significant reduction in the latency of SEPs. Histological analyses showed no signs of implant rejection; on the contrary, implants based on PPy improved the SEPs conduction and motor function after lesion.