Neurotoxicity in horses refers to the adverse effects on the nervous system caused by exposure to toxic substances. These substances can include environmental toxins, pharmaceuticals, or feed contaminants. Neurotoxic effects may manifest as behavioral changes, neurological deficits, or motor dysfunction. In horses, neurotoxicity can result from exposure to specific compounds such as lead, organophosphates, or certain plants. Identifying and understanding the sources and mechanisms of neurotoxicity are important for preventing and managing its impact on equine health. This page compiles peer-reviewed research studies and scholarly articles that explore the causes, mechanisms, and clinical implications of neurotoxicity in horses.
van Spijk JN, Beckmann K, Wehrli Eser M, Stirn M, Steuer AE, Saleh L, Schoster A.Neuro- and nephrotoxicity of polymyxins are known but clinical studies in horses are lacking. The aim of this study was to describe neurogenic and nephrogenic side effects of hospitalized horses receiving Polymyxin B (PolyB) as part of their treatment plan. Twenty horses diagnosed with surgical colic ( = 11), peritonitis ( = 5), typhlocolitis ( = 2), pneumonia, and pyometra (each = 1) were included. Antimicrobial treatment was randomized to GENTA (gentamicin 10 mg/kg bwt q24 h IV, penicillin 30.000 IU/kg q6 h IV) or NO GENTA (marbofloxacin 2 mg/kg bwt q24 h IV, penicillin 30.000 IU/kg q6 h IV...
Bamford NJ, Sprinkle SB, Cudmore LA, Cullimore AM, van Eps AW, Verdegaal EJMM, Tennent-Brown BS.Snake envenomation is a cause of morbidity and mortality in domestic animals worldwide. The clinical features of crotalid snake (pit viper) envenomation are widely reported and well described in horses but elapid snake envenomation is poorly characterised. Objective: To describe the presentation, clinical and laboratory findings, treatment and outcome of horses with a diagnosis of elapid snake envenomation in Australia. Methods: Retrospective case series. Methods: Medical records of horses with a diagnosis of elapid snake envenomation (2006-2016) at several university and private veterinary pr...
Domijan AM.Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium spp. moulds that contaminate crop, predominantly maize, all around the world. More than 15 types of fumonisins have been indentified so far, but FB(1) is the most abundant and toxicologically the most significant one. FB(1) has a wide range of toxic effects, depending on animal species. In horses FB(1) causes equine leukoencephalomalacia (ELEM), in pigs pulmonary oedema and in experimental rodents nephrotoxicity and hepatotoxicity. In humans exposure to FB(1) is linked with higher incidence of primary liver cancer and oesophageal cance...
Decloedt A, Verheyen T, De Clercq D, Sys S, Vercauteren G, Ducatelle R, Delahaut P, van Loon G.Horses are extremely susceptible to ionophore intoxication. Although numerous reports are available regarding monensin, little is known about lasalocid toxicity. Objective: To describe accidental lasalocid poisoning on a farm in Belgium. Methods: Eighty-one horses, of which 14 demonstrated clinical signs from day 0-21 after being fed a new concentrate batch. One horse died on day 20 and another on day 27. Methods: The most severe cases (n = 7), admitted to the clinic on day 29-46, underwent cardiac examination and blood biochemical analysis, including determination of plasma cardiac troponin...
Kovacić S, Pepeljnjak S, Petrinec Z, Klarić MS.For years scientists have suspected that the environment plays a role in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Mycotoxin fumonisin B1 (FB1) is produced by several Fusarium species, mainly by Fusarium verticilioides, which is one of the most common fungi associated with corn worldwide. Fumonisins are known to cause equine leukoencephalomalacia, a disease associated with the consumption of corn-based feeds contaminated with FB1. Here we have reported chronic experimental toxicosis in one-year-old carp (Cyprinus carpio L.) receiving f...
Barabas K, Milner R, Lurie D, Adin C.Cisplatin is a platinum chemotherapeutic used in a variety of malignancies. The antineoplastic activity occurs from DNA cross-links and adducts, in addition to the generation of superoxide radicals. Nephrotoxicity is the most well-known and potentially most clinically significant toxicity. Unfortunately, the mechanism for cisplatin nephrotoxicity has not been completely elucidated; however, many theories have been developed. Other toxicities include gastrointestinal, myelosuppression, ototoxicity and neurotoxicity. Saline diuresis is currently the most accepted way to prevent cisplatin nephrot...
Muzard J, Billiald P, Goyffon M, Aubrey N.Serotherapy is the only specific treatment for envenomation. The antibodies are obtained after the purification of serum from hyperimmunised horses and are used after fragmentation in the form of polyclonal Fab or F(ab)'2. The anti-venom sera are heterogeneous, and their protective effect is often weak. The administration of these preparations induces risks of immediate or delayed side effects: hypersensitivity reactions, anaphylactic shock and serum sickness. This observation led us to develop new forms of antibodies produced by molecular engineering, capable of specifically neutralizing the ...
Tukov FF, Rimoldi JM, Matthews JC.Repin, a major constituent in extracts of the plant Centaurea repens is thought to be the active principal responsible for the development of equine nigropallidal encephalomalacia (ENE), a fatal Parkinson-like neurodegenerative disorder in horses. Although the exact mechanism by which ingestion of this weed causes ENE is uncertain, a limited body of experimental evidence suggests a critical role for the glutathione redox system. In the present study, the mechanism of repin neurotoxicity was examined in PC12 cells with a focus on determining the role of glutathione (GSH) in repin-induced mitoch...
John HA, Laffling AJ, Marrs J, Baird A, Jat PS, Holdstock NB, Rossdale PD.To enable direct testing of a range of potential toxins or pathogens that might be involved in grass sickness, equine thoracic sympathetic chain ganglion cell lines were established from primary cell cultures by retroviral-mediated transduction of the temperature-sensitive mutant of the establishment oncogene encoding SV40 large T antigen. Morphological and behavioral features, temperature dependence, and immunocytochemical characteristics of the cell lines were investigated. The majority of cells were noradrenergic neurons in which dopamine-beta-hydroxylase, the enzyme that catalyzes norepine...
Uto A, Dux E, Hossmann KA.Glutamate neurotoxicity was studied in primary neuronal cultures prepared from rat cerebral cortex and hippocampal CA1 sector. Neurons were cultivated with 5% native horse serum and then exposed to 0.1 or 1.0 mM glutamate for 5 min. Subsequently, neurons were allowed to recover for 24 hours either in the presence or in the absence of 5% native horse serum. In the absence of serum, neurons showed morphological signs of degeneration and exhibited marked loss of vitality as tested by vital staining and release of lactate dehydrogenase (LDH). In contrast, when neurons were cultivated in the presen...
Szabo EA, Pemberton JM, Gibson AM, Thomas RJ, Pascoe RR, Desmarchelier PM.PCR for the detection of botulinum neurotoxin gene types A to E was used in the investigation of a case of equine botulism. Samples from a foal diagnosed with toxicoinfectious botulism in 1985 were reanalyzed by PCR and the mouse bioassay in conjunction with an environmental survey. Neurotoxin B was detected by mouse bioassay in culture enrichments of serum, spleen, feces, and intestinal contents. PCR results compared well with mouse bioassay results, detecting type B neurotoxin genes in these samples and also in a liver sample. Other neurotoxin types were not detected by either test. Clostrid...
Gaynor JS, Hubbell JA.Local and regional anesthetic techniques are useful tools for the equine practitioner. These techniques allow surgery to be performed without the risk and cost of general anesthesia. There are, however, risks associated with the local and regional techniques. Neurotoxicity, although rare, may occur when 200 mL or more of a local anesthetic are infiltrated in a short period of time to a 450-kg horse. More likely, horses may become ataxic after nerve blockade in the limbs. This ataxia may lead to self trauma because the horse may not know where the limbs are actually being placed. Although local...
Fleming JT, Joshi JG.We previously showed that human brain ferritin (HBF) binds aluminum (Al) in vivo and in vitro and HBF isolated from Alzheimer's brain had more Al bound compared to aged matched controls (7). To further understand the role ferritin may play in Al neurotoxicity, we have studied in vitro the effect of Al on the function of human ferritin isolated from Alzheimer's (AD) and normal brain tissue, and compared the results with other mammalian ferritins. Al causes a concentration-dependent decrease in the initial rate of iron loading into apo-horse spleen and human brain ferritin and the rates were sim...
Pemberton AD, Hodgson JC, Gilmour JS, Doxey DL.Isolates were prepared from the sera of 12 horses with acute grass sickness, using methods reported to yield serum fractions associated with neurotoxicity, and their components identified by liquid chromatography and spectroscopy. All isolates were found to contain cortisol and six isolates also contained a degradation product of an analgesic drug, dipyrone. However, no recognised neurotoxin was detected.
Johnson P.An unusual compound of small molecular weight has been detected in serum from horses with acute grass sickness by solvent extractions and thin-layer chromatography. The substance has not been detected in the serum of normal horses or cases of equine colic and apparently disappears from grass sickness serum after two to three days of clinical illness. Although this compound is found in sera which are known to possess in vivo neurotoxicity, this property could not be demonstrated in either the total chloroform extract which contains the compound or in the hydrophilic serum components remaining a...
Gilmour JS, Mould DL.Plasma, serum and cells were prepared from blood taken from acute cases of grass sickness, and plasma was fractionated by gel filtration and salt precipatation. These preparations were all tested for neurotoxic activity by injection into ponies. Plasma and serum were found to produce the neurohistological changes seen in grass sickness, as was a plasma protein fraction of molecular weight 30,000 or greater. Activity was retained following storage at--75 degrees C for 15 months. Plasma given orally to a pony produced no detectable effect, nor was activity demonstrated following the injection of...
Fitzgerald WE.Four cases of snakebite in horses are presented. Diagnosis was made on clinical signs in all, plus fang punctures in 2 cases. Tiger snake antivenene was used in the treatment of 2 patients and these recovered rapidly. Of the 2 in which antivenene was not used, 1 severely affected horse died. The clinical signs which were observed were those of progressive general paralysis and were entirely referable to the neurotoxic component of the venom.
Barabas K, Milner R, Lurie D, Adin C.Cisplatin is a platinum chemotherapeutic used in a variety of malignancies. The antineoplastic activity occurs from DNA cross-links and adducts, in addition to the generation of superoxide radicals. Nephrotoxicity is the most well-known and potentially most clinically significant toxicity. Unfortunately, the mechanism for cisplatin nephrotoxicity has not been completely elucidated; however, many theories have been developed. Other toxicities include gastrointestinal, myelosuppression, ototoxicity and neurotoxicity. Saline diuresis is currently the most accepted way to prevent cisplatin nephrot...
Domijan AM.Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium spp. moulds that contaminate crop, predominantly maize, all around the world. More than 15 types of fumonisins have been indentified so far, but FB(1) is the most abundant and toxicologically the most significant one. FB(1) has a wide range of toxic effects, depending on animal species. In horses FB(1) causes equine leukoencephalomalacia (ELEM), in pigs pulmonary oedema and in experimental rodents nephrotoxicity and hepatotoxicity. In humans exposure to FB(1) is linked with higher incidence of primary liver cancer and oesophageal cance...
Tukov FF, Rimoldi JM, Matthews JC.Repin, a major constituent in extracts of the plant Centaurea repens is thought to be the active principal responsible for the development of equine nigropallidal encephalomalacia (ENE), a fatal Parkinson-like neurodegenerative disorder in horses. Although the exact mechanism by which ingestion of this weed causes ENE is uncertain, a limited body of experimental evidence suggests a critical role for the glutathione redox system. In the present study, the mechanism of repin neurotoxicity was examined in PC12 cells with a focus on determining the role of glutathione (GSH) in repin-induced mitoch...
Szabo EA, Pemberton JM, Gibson AM, Thomas RJ, Pascoe RR, Desmarchelier PM.PCR for the detection of botulinum neurotoxin gene types A to E was used in the investigation of a case of equine botulism. Samples from a foal diagnosed with toxicoinfectious botulism in 1985 were reanalyzed by PCR and the mouse bioassay in conjunction with an environmental survey. Neurotoxin B was detected by mouse bioassay in culture enrichments of serum, spleen, feces, and intestinal contents. PCR results compared well with mouse bioassay results, detecting type B neurotoxin genes in these samples and also in a liver sample. Other neurotoxin types were not detected by either test. Clostrid...
Fleming JT, Joshi JG.We previously showed that human brain ferritin (HBF) binds aluminum (Al) in vivo and in vitro and HBF isolated from Alzheimer's brain had more Al bound compared to aged matched controls (7). To further understand the role ferritin may play in Al neurotoxicity, we have studied in vitro the effect of Al on the function of human ferritin isolated from Alzheimer's (AD) and normal brain tissue, and compared the results with other mammalian ferritins. Al causes a concentration-dependent decrease in the initial rate of iron loading into apo-horse spleen and human brain ferritin and the rates were sim...
Kovacić S, Pepeljnjak S, Petrinec Z, Klarić MS.For years scientists have suspected that the environment plays a role in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Mycotoxin fumonisin B1 (FB1) is produced by several Fusarium species, mainly by Fusarium verticilioides, which is one of the most common fungi associated with corn worldwide. Fumonisins are known to cause equine leukoencephalomalacia, a disease associated with the consumption of corn-based feeds contaminated with FB1. Here we have reported chronic experimental toxicosis in one-year-old carp (Cyprinus carpio L.) receiving f...
Gilmour JS, Mould DL.Plasma, serum and cells were prepared from blood taken from acute cases of grass sickness, and plasma was fractionated by gel filtration and salt precipatation. These preparations were all tested for neurotoxic activity by injection into ponies. Plasma and serum were found to produce the neurohistological changes seen in grass sickness, as was a plasma protein fraction of molecular weight 30,000 or greater. Activity was retained following storage at--75 degrees C for 15 months. Plasma given orally to a pony produced no detectable effect, nor was activity demonstrated following the injection of...
Pemberton AD, Hodgson JC, Gilmour JS, Doxey DL.Isolates were prepared from the sera of 12 horses with acute grass sickness, using methods reported to yield serum fractions associated with neurotoxicity, and their components identified by liquid chromatography and spectroscopy. All isolates were found to contain cortisol and six isolates also contained a degradation product of an analgesic drug, dipyrone. However, no recognised neurotoxin was detected.
Johnson P.An unusual compound of small molecular weight has been detected in serum from horses with acute grass sickness by solvent extractions and thin-layer chromatography. The substance has not been detected in the serum of normal horses or cases of equine colic and apparently disappears from grass sickness serum after two to three days of clinical illness. Although this compound is found in sera which are known to possess in vivo neurotoxicity, this property could not be demonstrated in either the total chloroform extract which contains the compound or in the hydrophilic serum components remaining a...
John HA, Laffling AJ, Marrs J, Baird A, Jat PS, Holdstock NB, Rossdale PD.To enable direct testing of a range of potential toxins or pathogens that might be involved in grass sickness, equine thoracic sympathetic chain ganglion cell lines were established from primary cell cultures by retroviral-mediated transduction of the temperature-sensitive mutant of the establishment oncogene encoding SV40 large T antigen. Morphological and behavioral features, temperature dependence, and immunocytochemical characteristics of the cell lines were investigated. The majority of cells were noradrenergic neurons in which dopamine-beta-hydroxylase, the enzyme that catalyzes norepine...
Fitzgerald WE.Four cases of snakebite in horses are presented. Diagnosis was made on clinical signs in all, plus fang punctures in 2 cases. Tiger snake antivenene was used in the treatment of 2 patients and these recovered rapidly. Of the 2 in which antivenene was not used, 1 severely affected horse died. The clinical signs which were observed were those of progressive general paralysis and were entirely referable to the neurotoxic component of the venom.
van Spijk JN, Beckmann K, Wehrli Eser M, Stirn M, Steuer AE, Saleh L, Schoster A.Neuro- and nephrotoxicity of polymyxins are known but clinical studies in horses are lacking. The aim of this study was to describe neurogenic and nephrogenic side effects of hospitalized horses receiving Polymyxin B (PolyB) as part of their treatment plan. Twenty horses diagnosed with surgical colic ( = 11), peritonitis ( = 5), typhlocolitis ( = 2), pneumonia, and pyometra (each = 1) were included. Antimicrobial treatment was randomized to GENTA (gentamicin 10 mg/kg bwt q24 h IV, penicillin 30.000 IU/kg q6 h IV) or NO GENTA (marbofloxacin 2 mg/kg bwt q24 h IV, penicillin 30.000 IU/kg q6 h IV...
Uto A, Dux E, Hossmann KA.Glutamate neurotoxicity was studied in primary neuronal cultures prepared from rat cerebral cortex and hippocampal CA1 sector. Neurons were cultivated with 5% native horse serum and then exposed to 0.1 or 1.0 mM glutamate for 5 min. Subsequently, neurons were allowed to recover for 24 hours either in the presence or in the absence of 5% native horse serum. In the absence of serum, neurons showed morphological signs of degeneration and exhibited marked loss of vitality as tested by vital staining and release of lactate dehydrogenase (LDH). In contrast, when neurons were cultivated in the presen...
Bamford NJ, Sprinkle SB, Cudmore LA, Cullimore AM, van Eps AW, Verdegaal EJMM, Tennent-Brown BS.Snake envenomation is a cause of morbidity and mortality in domestic animals worldwide. The clinical features of crotalid snake (pit viper) envenomation are widely reported and well described in horses but elapid snake envenomation is poorly characterised. Objective: To describe the presentation, clinical and laboratory findings, treatment and outcome of horses with a diagnosis of elapid snake envenomation in Australia. Methods: Retrospective case series. Methods: Medical records of horses with a diagnosis of elapid snake envenomation (2006-2016) at several university and private veterinary pr...
Gaynor JS, Hubbell JA.Local and regional anesthetic techniques are useful tools for the equine practitioner. These techniques allow surgery to be performed without the risk and cost of general anesthesia. There are, however, risks associated with the local and regional techniques. Neurotoxicity, although rare, may occur when 200 mL or more of a local anesthetic are infiltrated in a short period of time to a 450-kg horse. More likely, horses may become ataxic after nerve blockade in the limbs. This ataxia may lead to self trauma because the horse may not know where the limbs are actually being placed. Although local...
Decloedt A, Verheyen T, De Clercq D, Sys S, Vercauteren G, Ducatelle R, Delahaut P, van Loon G.Horses are extremely susceptible to ionophore intoxication. Although numerous reports are available regarding monensin, little is known about lasalocid toxicity. Objective: To describe accidental lasalocid poisoning on a farm in Belgium. Methods: Eighty-one horses, of which 14 demonstrated clinical signs from day 0-21 after being fed a new concentrate batch. One horse died on day 20 and another on day 27. Methods: The most severe cases (n = 7), admitted to the clinic on day 29-46, underwent cardiac examination and blood biochemical analysis, including determination of plasma cardiac troponin...
Muzard J, Billiald P, Goyffon M, Aubrey N.Serotherapy is the only specific treatment for envenomation. The antibodies are obtained after the purification of serum from hyperimmunised horses and are used after fragmentation in the form of polyclonal Fab or F(ab)'2. The anti-venom sera are heterogeneous, and their protective effect is often weak. The administration of these preparations induces risks of immediate or delayed side effects: hypersensitivity reactions, anaphylactic shock and serum sickness. This observation led us to develop new forms of antibodies produced by molecular engineering, capable of specifically neutralizing the ...
