Cat Brain Research Articles

Gyration of the feline brain: localization, terminology and variability.

The terminology of feline brain gyration is not consistent and individual variability has not been systematically examined. The aim of the study was to identify the gyri and sulci of cat brains and describe them using the current terminology. The brains of 15 cats including 10 European shorthairs, 2 Siamese, 2 Maine coons and one Norvegian forest cat without clinical evidence of brain disease were examined post-mortem and photographed for documentation. For description, the terms of the most recent Nomina Anatomica Veterinaria (NAV, 2012) were used, and comparisons with previous anatomical texts were also performed. In addition to the lack of comparative morphology in the NAV, veterinary and human nomenclature are used interchangeably and inconsistently in the literature. This presents a challenge for neurologists and anatomists in localizing gyri and sulci. A comparative analysis of brain gyration showed only minor individual variability among the cats. High-quality labelled figures are provided to facilitate the identification of cat brain gyration. Our work consolidates the current and more consistent gyration terminology for reporting the localization of a cortical lesion based on magnetic resonance imaging or histopathology. This will facilitate not only morphological but also functional research using accurate anatomical reporting.

Prominent hypointense veins on susceptibility weighted image in the cat brain with acute infarction: DWI, SWI, and PWI

The multiple prominent hypointense veins on susceptibility-weighted imaging (SWI) have been found in the ischemic territory of patients with acute ischemic stroke. Venous side is the unknown area in the hemodynamics of brain infarction. To evaluate the venous aspect in acute brain infarction through an animal study. The acute infarction in cat brains was induced with a bolus infusion of 0.25 mL of triolein through one side of the common carotid artery. The magnetic resonance (MR) images, including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, SW, and perfusion-weighted (PWI) images, were obtained serially at 2 h (n = 17), 1 day (n = 11), and 4 days (n = 4) after triolein infusion. The obtained MR images were evaluated qualitatively and quantitatively. For qualitative assessment, the signal intensity of the serial MR images was evaluated. The presence or absence and the location with serial changes of infarction were identified on DWI and ADC map images. The presence or absence of prominent hypointense veins and the serial changes of cortical veins were also evaluated on SWI. Quantitative assessment was performed by comparing the relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit times (MTT) of the lesions with those of the contralateral normal side calculated on PWI. The serial changes of rCBV, rCBF, and MTT ratio were also evaluated. Acute infarction in the first and second medial gyrus of lesion hemisphere was found by qualitative evaluation of DWI and ADC map images. On the serial evaluation of SWI, the cortical veins of cat brain with infarction were obscured at 2 h and then re-appeared at 1 day. The hemorrhage transformation and prominent hypointense veins were seen at 4 days on SWI. The quantitative evaluation revealed increased MTT ratios and decreased rCBV and rCBF ratios on PWIs in the acute infarction of cat brain. The prominent hypointense veins on SWI were seen in the half of the acute infarction at 4 days. The prominent hypointense veins on SWI may have good agreement with the increased MTT ratio.

Isolation and molecular characterization of Toxoplasma gondii isolated from pigeons and stray cats in Lisbon, Portugal

Cats and pigeons are important factors in the epidemiology of Toxoplasma gondii as felids are the only definitive hosts that can excrete environmentally resistant oocysts, and pigeons share the same places of cats and humans constituting a good model and indicator of the ground field contamination. We aimed to study the virulence and genotypes of T. gondii isolated from pigeons and stray cats in Lisbon, Portugal. Fresh samples of brain from 41 pigeons and 164 cats revealing antibodies to T. gondii were inoculated in mice. Three isolates (one isolated from a cat and two isolated from pigeons) were virulent in the mouse model. Sag2-based genotyping of T. gondii was achieved in 70.7% (29/41) of samples isolated from pigeons (26 samples were type II, two were type III, and one strain was type I). From the cat brain samples, 50% (82/164) yielded Sag2 positive results, where 72 belonged to genotype II and 10 were no type III (it was not possible to discriminate between type I and II). Further genotyping was obtained by multiplex PCR of 5 microsatellites (TUB2, TgM-A, W35, B17, B18), allowing the identification of two recombinant strains that had been previously identified as type II by Sag2 amplification (one isolated from cat brain and the other from pigeon brain). This is the first evidence of recombinant strains circulating in Portugal and the first report of T. gondii genotyping from cats in this country. This study also highlights the importance of environmental contamination in the synanthropic cycle constituting a potential source of human infection.

Seropathological Diagnosis of Toxoplasma gondii in Stray Cats in Baghdad Province

The current study was performed an investigation in seropositive stray cats with Toxoplasma gondii and to correlate the results of pathological lesions with seropositive results of the cats. To achieve these goals, fifty blood samples and specimens from internal organs (liver, spleen, brain, kidney, intestine and lung) of stray cats were collected from different area of Baghdad Province during the period 1.10.2011-1.10.2012. Seropositive ELISA-IgG was demonstrated that 66 % of stray cats while female expressed (75 %) of seropositive ELISA-IgG were higher than male (30% ) and animals with average age 2months showed high percentage of seropositive ELISA-IgG (100%) as compared with age (adult cat) that expressed( 63.82 %) of seropositive. There was a significant difference (P≤0.01) among positive cases to anti-Toxoplasma ELISA-IgG. Severe pathological lesions were noticed in the lungs ,livers and intestines of animals that expressed high (optical density) (OD) of anti-Toxoplasma IgG ,in addition ,tachyzoits intracytoplasm of alveolar macrophages and hepatocytes as well as free zoites in alveolar space of the lung, were reported. Local necrosis with tachyzoites was seen in the brain of the cats, in addition to mineralization. On bases of the presence of pathological lesions in cats that expressed seropositive anti-Toxoplasma antibodies, it can be conclude that T.gondii is responsible for the appearance of inflammatory reaction in the internal organs of cats and there is a correlation between seropositive and pathological lesions of T.gondii infection and this parasite is highly distributed in Baghdad stray cats and it may be an important cause of abortion in the women.

IgG and Complement Deposition and Neuronal Loss in Cats and Humans With Epilepsy and Voltage-Gated Potassium Channel Complex Antibodies

Voltage-gated potassium channel complex (VGKC-complex) antibody (Ab) encephalitis is a well-recognized form of limbic encephalitis in humans, usually occurring in the absence of an underlying tumor. The patients have a subacute onset of seizures, magnetic resonance imaging findings suggestive of hippocampal inflammation, and high serum titers of Abs against proteins of the VGKC-complex, particularly leucine-rich, glioma-inactivated 1 (LGI1). Most patients are diagnosed promptly and recover substantially with immunotherapies; consequently, neuropathological data are limited. We have recently shown that feline complex partial cluster seizures with orofacial involvement (FEPSO) in cats can also be associated with Abs against VGKC-complexes/LGI1. Here we examined the brains of cats with FEPSO and compared the neuropathological findings with those in a human with VGKC-complex-Ab limbic encephalitis. Similar to humans, cats with VGKC-complex-Ab and FEPSO have hippocampal lesions with only moderate T-cell infiltrates but with marked IgG infiltration and complement C9neo deposition on hippocampal neurons, associated with neuronal loss. These findings provide further evidence that FEPSO is a feline form of VGKC-complex-Ab limbic encephalitis and provide a model for increasing understanding of the human disease.

Principles of age-related changes in the canine and feline brain

Abstract In the aged dog and cat, especially dog, a cognitive decline develops naturally in many different domains, but at the same time it also exhibits human-like individual variability in the aging process. In the aging dog and cat brain lesions develop spontaneously. Dogs share some morphological characteristics with those of Alzheimer’s disease in man. The canine brain with its plaques and tangles which show oxidative changes, forms a spontaneous model for understanding the early changes and their interrelationships in Alzheimer’s disease. Additionally, the aged dog represents a useful model for the development of preventive or therapeutic interventions to improve aged brain function. These interventions can then be translated into human clinical trials.

Measurement of Ultrasonic Attenuation in Diabetic Neuropathic Sciatic Nerves for Diagnostic and Therapeutic Applications

Measurements of ultrasonic attenuation in the sciatic nerves of rats were performed to verify the feasibility of ultrasound diagnosis of peripheral neuropathy and to avoid damage to the nerves caused by overheating in pain management applications. A rat model of diabetic peripheral neuropathy was established. The proximal-segment and middle-segment sciatic nerves of control and neuropathic rats were dissected for the attenuation measurement. Two commercial ultrasound transducers and a self-developed experimental platform were used in the measurements. Using H&E staining and transmission electron (TE) microscopy, morphological analysis of the control and neuropathic nerves was performed to determine the relationship between attenuation and the histology of the nerves. The experimental results showed that the attenuation coefficients of the control, second-week, fourth-week, and eighth-week neuropathic nerves were -6.68 ± 0.50, -5.61 ± 0.34, -6.27 ± 0.40, and -7.10 ± 0.35 dB/cm at 2.68 MHz, respectively. The respective values at 7.50 MHz were -14.96 ± 0.79, -12.65 ± 0.28, -13.98 ± 1.07, and -16.00 ± 0.54 dB/cm. The changes in the attenuation coefficients were significantly different among the second-week, fourth-week, and eighth-week DN nerves. Additionally, the ultrasonic attenuation coefficient of the rat sciatic nerve was fourfold that of the cat brain and cow liver and twofold that of human muscle.

Quantitative, noninvasive, in vivo longitudinal monitoring of gene expression in the brain by co-AAV transduction with a PET reporter gene

In vivo imaging of vector transgene expression would be particularly valuable for repetitive monitoring of therapy in the brain, where invasive tissue sampling is contraindicated. We evaluated adeno-associated virus vector expression of a dopamine-2 receptor (D2R) mutant (D2R80A) by positron emission tomography in the brains of mice and cats. D2R80A is inactivated for intracellular signaling and binds subphysiologic amounts of the radioactive [18F]-fallypride analog of dopamine. The [18F]-fallypride signal bound to D2R80A in the injection site was normalized to the signal from endogenous D2R in the striatum and showed stable levels of expression within individual animals. A separate adeno-associated virus type 1 vector with identical gene expression control elements, expressing green fluorescent protein or a therapeutic gene, was coinjected with the D2R80A vector at equal doses into specific sites. Both transgenes had similar levels of gene expression by immunohistochemistry, in situ hybridization, and quantitative PCR assays, demonstrating that D2R80A is a faithful surrogate measure for expression of a gene of interest. This dual vector approach allows the D2R80A gene to be used with any therapeutic gene and to be injected into a single site for monitoring while the therapeutic gene can be distributed more widely as needed in each disease.

Effects of Strabismus and Monocular Deprivation on the Sizes of Callosal Cells in Cortical Fields 17 and 18 in the Cat Brain

Structural changes in the visual cortex were studied in conditions of deranged binocular experience by assessing the sizes (body areas) of callosal cells in fields 17 and 18 in monocularly deprived cats and in cats with convergent strabismus. These cells were detected by injection of horseradish peroxidase into columns in cortical fields 17 and 18 and the fields 17/18 transitional zone. In both groups, the mean size of callosal cells in field 17 was greater than normal, though this difference in field 18 was seen only in monocularly deprived cats. Differences in the mean sizes of field 17 and 18 cells in cats of the study groups were found to be due to the number of large cells. In cats with strabismus, callosal cells of size greater than 200 μm2 accounted for 58% of cells in field 17 and 8% in field 18. In monocularly deprived cats, there was no difference in the proportions of large callosal cells in these fields (28% and 26%, respectively). These data provide evidence that cytoarchitectonic changes occurred in layers of the visual cortex, serving as sources of interhemisphere connections, in conditions of early derangement of binocular experience.

Tissue distribution of human and avian type sialic acid influenza virus receptors in domestic cat

Infection of host cells with the influenza virus is mediated by specific interactions between the viral haemagglutinin (HA) and cell oligosaccharides containing sialic acid (SA) residues. Avian and human influenza viruses bind to alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors, respectively. To date, there have been no detailed tissue distribution data on alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors in the domestic cat, a relatively new mammalian host for influenza virus infections. In this study, the tissue distribution of human and avian type sialic acid influenza receptors was determined in various organs (respiratory tract, gastrointestinal tract, brain, cerebellum, spleen, kidney, heart and pancreas) of domestic cat by binding with the lectins Maackia amurensis agglutinin II (MAA II) and Sambucus nigra agglutinin (SNA), respectively. The results revealed that both alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors were extensively detected in the trachea, bronchus, lung, kidney, spleen, pancreas and gastrointestinal tract. Endothelial cells of gastrointestinal tract organs were negative for alpha-2, 3 sialic acid-linked receptors in cats. The presence of alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors in the major organs examined in the present study suggests that each major organ may be affected by influenza virus infection. Because of receptor distribution in the gastrointestinal tract, the experimental infection of cats with human influenza virus may be relatively easy while their infection with avian influenza virus may be difficult. These data can explain the involvement of multiple organs in influenza virus infection and should help investigators interpret the results obtained when cats are infected with influenza virus and estimate the risk of infection between cats and humans.

Hemorrhage in cerebral fat embolisms in a cat model using triolein dependent on the physical properties of triolein

Hemorrhage is a finding of clinical fat embolism syndrome. The purpose of the present study was to evaluate the occurrence of hemorrhage in the cat brain by SW MR imaging after infusion of triolein as a bolus or as an emulsion into the carotid artery. Twenty-two cats were divided into two groups according to the type of triolein infused: group 1 (n = 11) was infused with a 0.1 ml triolein bolus, group 2 (n = 11) with triolein emulsion containing 0.1 ml triolein in 20 ml saline. SW imaging was performed before and after triolein infusion (at 2 h, 1 and 4 days). After MR imaging on day 4, cats were sacrificed and brains were immediately excised. Hemorrhage was evaluated using H&E staining. Hemorrhage was observed in eight cats in group 1, in no cats in group 2. Hemorrhage on SW images was found to correspond with light microscopy. SW images revealed hemorrhage in lesion hemispheres infused with triolein bolus. However, there was no evidence of hemorrhage infused with emulsified triolein. Thus, the occurrence of hemorrhage in cerebral fat embolism may depend on fat status.

A multispectral LED array for the reduction of background autofluorescence in brain tissue

The presence of fixative-induced and cellular-derived artifactual autofluorescences (AAFs) presents a challenge in histological analysis involving immunofluorescence. We have established a simple and highly effective method for the reduction of AAFs that are ubiquitous in fixed mammalian brain and other tissues. A compact AAF-quenching photo-irradiation device was constructed using a commercially available light emitting diode (LED) array, cooling unit, and supporting components. The LED panel is comprised of an array of multispectral high intensity LEDs which serve as the illumination source for the photo-irradiation process. Rabbit and cat brain specimens of 5μm- and 40μm-thicknesses, respectively, were photo-irradiated for various durations. The AAFs were reduced to near tissue background levels after 24h of treatment for both deparaffinized and paraffinized rabbit brain specimens, and for the free-floating cat brain specimens. Subsequent immunofluorescence staining using primary antibodies against GFAP, NeuN, Iba-1, and MAP-2, and the corresponding Qdot® and Alexafluor® fluoroconjugates confirmed that the LED photo-irradiation treatment did not compromise the efficiency of the immunofluorescence labeling. The use of the device is not labor intensive, and only requires minimal tissue processing and experimental set-up time, with very low maintenance and operating costs. Finally, multiple specimens, in both slide and well-plate format, can be simultaneously photo-irradiated, thus, allowing for scalable batch processing.

The influence of the tracer injection–acquisition interval on the distribution of 99mTc-ECD in the brain of laboratory cats

Abstract Single-photon emission computed tomography (SPECT) can be used to study the regional distribution of the cerebral blood flow in the feline brain without interference of anesthetics. When the tracer, 99m technetium-ethyl cysteinate dimer ( 99m Tc-ECD), is injected in the awake animal, the acquisition can be performed afterward under general anesthesia, whereas the tracer distribution still represents the regional cerebral blood flow (rCBF) in the awake animal. The aim of this study was to look at the in vivo stability of 99m Tc-ECD in the feline brain. For this purpose, 6 cats (n = 6) were used, and 3 serial acquisitions were performed starting at 40 (T40), 60 (T60), and 85 (T85) minutes after tracer injection. Total counts and perfusion indices (PIs), normalized to the total brain and to the cerebellum, were calculated. When T85 was compared with T40, total counts decreased, depending on the brain region, with 29% (left thalamus) to 51% (bulbus olfactorius). These regional differences in tracer clearance resulted in significantly altered PIs at T85 as compared with T40. This study shows that 99m Tc-ECD SPECT can be used in cats for studying the rCBF and that the clearance of 99m Tc-ECD in the feline brain is region dependent. As a result, the acquisition should be started between 40 and 60 minutes after tracer injection.

Intracellular redox state revealed by in vivo 31P MRS measurement of NAD+ and NADH contents in brains

Nicotinamide adenine dinucleotide (NAD), in oxidized (NAD(+) ) or reduced (NADH) form, plays key roles in cellular metabolism. Intracellular NAD(+) /NADH ratio represents the cellular redox state; however, it is difficult to measure in vivo. We report here a novel in vivo (31) P MRS method for noninvasive measurement of intracellular NAD concentrations and NAD(+) /NADH ratio in the brain. It uses a theoretical model to describe the NAD spectral patterns at a given field for quantification. Standard NAD solutions and independent cat brain measurements at 9.4 T and 16.4 T were used to evaluate this method. We also measured T1 values of brain NAD. Model simulation and studies of solutions and brains indicate that the proposed method can quantify submillimolar NAD concentrations with reasonable accuracy if adequate (31) P MRS signal-to-noise ratio and linewidth were obtained. The NAD concentrations and NAD(+) /NADH ratio of cat brains measured at 16.4 T and 9.4 T were consistent despite the significantly different T1 values and NAD spectra patterns at two fields. This newly established (31) P MRS method makes it possible for the first time to noninvasively study the intracellular redox state and its roles in brain functions and diseases, and it can potentially be applied to other organs.

Multiobjective Identification of Controlling Areas in Neuronal Networks

In this paper, we investigate the multiobjective identification of controlling areas in the neuronal network of a cat's brain by considering two measures of controllability simultaneously. By utilizing nondominated sorting mechanisms and composite differential evolution (CoDE), a reference-point-based nondominated sorting composite differential evolution (RP-NSCDE) is developed to tackle the multiobjective identification of controlling areas in the neuronal network. The proposed RP-NSCDE shows its promising performance in terms of accuracy and convergence speed, in comparison to nondominated sorting genetic algorithms II. The proposed method is also compared with other representative statistical methods in the complex network theory, single objective, and constraint optimization methods to illustrate its effectiveness and reliability. It is shown that there exists a tradeoff between minimizing two objectives, and therefore pareto fronts (PFs) can be plotted. The developed approaches and findings can also be applied to coordination control of various kinds of real-world complex networks including biological networks and social networks, and so on.

Location of cat brain stem neurons that drive sweating

The brain stem premotor pathways controlling most noncardiovascular sympathetic outflows are unknown. Here, we mapped the brain stem neurons that drive sweating, by microinjecting excitant amino acid (L-glutamate or D,L-homocysteate: 0.4-3 nmol) into 420 sites over the pons and medulla of eight chloralose-anesthetized cats (70 mg/kg iv). Sweating was recorded by the electrodermal potential at the ipsilateral forepaw pad. Responses were classified as immediate (<5 s latency) or delayed (>10 s latency). Immediate responses were obtained from 16 sites (1-3 per animal) and were accompanied by no change in blood pressure. Those sites were clustered between the facial nucleus and the pyramidal tract in the rostral ventromedial medulla (RVMM). Microinjections into 33 surrounding sites caused delayed electrodermal responses of lesser amplitude, while the remaining 371 sites evoked none. To retrogradely label bulbospinal neurons that may mediate electrodermal responses, fluorescent latex microspheres were injected into the region of the intermediolateral cell column in the fourth thoracic segment in an earlier preparatory procedure on six of the animals. A cluster of retrogradely labeled neurons was identified between the facial nucleus and the pyramidal tract. Neurons in this discrete region of the RVMM, thus, drive sweating in the cat's paw and may do so via direct spinal projections.

Form and function of arterial bifurcations in various parts of the animal body

Branching patterns of arterial networks might influence vascular resistance and allow control of blood supply to peripheral tissues. Arterial casts from the brain, kidneys, and earlobes of cats and the chorioallantoic arteries of chick embryos were used for microscopic measurements of arterial geometry. From the measured diameters of parent and two daughter vessels at arterial bifurcations, we calculated the diameter exponent m. By applying the minimum work concept to blood flow through a cylindrical vessel, an optimal value m = 3 has been derived (Murray's cubic law). The measured values of the diameter exponent were 2.59, 2.54, 2.58, and 2.49 for the brain, kidneys, earlobes, and chick embryos, respectively, exhibiting significant deviation from Murray's law. The physiological implication of the m values is discussed here.

Relating cytoarchitectonic differentiation and interareal distance to corticocortical connection patterns in the cat brain

Information processing in the brain is constrained by structural connectivity on multiple scales. However, the principles governing the organization of corticocortical connectivity, particularly the existence, density and laminar origin and termination patterns of projections, remain elusive. Here, we tested three models of relationships between the organization of cortical structure and features of connections linking 48 areas in the cat cerebral cortex. Factors taken into account were the relative cytoarchitectonic differentiation (structural model), relative spatial position (distance model), and relative hierarchical position (hierarchical model) of cortical areas.

MPTP Animal Model of Parkinsonism: Dopamine Cell Death or Only Tyrosine Hydroxylase Impairment? – A Study Using PET Imaging, Autoradiography, and Immunohistochemistry in the Cat

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin widely used to produce experimental models of Parkinson's disease in laboratory animals. It is believed to cause a selective destruction of substantia nigra dopamine neurons, mainly based on a large reduction of tyrosine hydroxylase (TH), the catecholamine's synthesizing enzyme. Unlike Parkinson's disease in humans, however, all animal models are able to recover more or less rapidly from the MPTP induced Parkinsonian syndrome. This raises the question as whether MPTP causes a cell death with a decrease in dopamine transporter or a simple impairment of TH. To respond to this question, we quantified in a cat model of Parkinson's disease (MPTP 5mg/kg i.p. during 5days) the dopamine transporter using positron emission tomography (PET) imaging and autoradiography of [(11) C]PE2I and compared the data with the TH-immunoreactivity. We found no changes in [(11) C]PE2I PET binding either 5 or 26days after MPTP treatment when compared to baseline levels. Similarly, there were no significant changes in [(11) C]PE2I autoradiographic binding in the cat brain one week after MPTP treatment. In sharp contrast, MPTP treated cats exhibited severe Parkinson-like motor syndrome during the acute period with a marked decrease in TH-immunoreactivity in the striatum. These data suggest that MPTP toxicity impairs efficiently TH and that such an effect is not necessarily accompanied by significant reduction of dopamine transporter seen with in vitro or in vivo [(11) C]PE2I binding.

Neurofibrillary Tangles and the Deposition of a Beta Amyloid Peptide with a Novel N-Terminal Epitope in the Brains of Wild Tsushima Leopard Cats

Beta amyloid (Aβ) deposits are seen in aged individuals in many of the mammalian species that possess the same Aβ amino acid sequence as humans. Conversely, neurofibrillary tangles (NFT), the other hallmark lesion of Alzheimer’s disease (AD), are extremely rare in these animals. We detected Aβ deposits in the brains of Tsushima leopard cats (Prionailurus bengalensis euptilurus) that live exclusively on Tsushima Island, Japan. Aβ42 was deposited in a granular pattern in the neuropil of the pyramidal cell layer, but did not form argyrophilic senile plaques. These Aβ deposits were not immunolabeled with antibodies to the N-terminal of human Aβ. Sequence analysis of the amyloid precursor protein revealed an amino acid substitution at the 7th residue of the Aβ peptide. In a comparison with other mammalian animals that do develop argyrophilic senile plaques, we concluded that the alternative Aβ amino acid sequence displayed by leopard cats is likely to be related to its distinctive deposition pattern. Interestingly, most of the animals with these Aβ deposits also developed NFTs. The distributions of hyperphosphorylated tau-positive cells and the two major isoforms of aggregated tau proteins were quite similar to those seen in Alzheimer’s disease. In addition, the unphosphorylated form of GSK-3β colocalized with hyperphosphorylated tau within the affected neurons. In conclusion, this animal species develops AD-type NFTs without argyrophilic senile plaques.