Identification of degenerated synaptic boutons in the dorsal claustrum of the cat after electrolytic lesions of the intralaminar thalamic nuclei.

The aim of this study is to investigate whether the dorsal claustrum receives afferent input from the intralaminar thalamic nuclei - centromedian nucleus, central lateral nucleus and paracentral nucleus. The intralaminar thalamic nuclei of eight cats were electrolytically lesioned. We obtained samples from the dorsal claustrum for electron microscopic analysis from the second to the seventh post-procedural day. Two types of degenerated synaptic boutons were observed: electron-dense which formed the majority of boutons, and electron-lucent comprising the remaining samples. Between the second and seventh post-procedural day, we observed a steady increase in the number of electron-dense boutons which were diffusely distributed throughout the dorsal claustrum. Electron-dense degenerated boutons formed asymmetrical contacts with dendritic spines as well as with small and medium-sized dendrites. In contrast, electron-lucent degenerated boutons were observed in earlier post-procedural periods and formed symmetrical axodendritic contacts.

The vascular footprint in cardiac homeostasis and hypertensive heart disease-A link between apelin receptor, vascular endothelial growth factor, and neuronal nitric oxide synthase.

Recent studies have suggested a connection between disturbances of the apelin system and various cardiac pathologies, including hypertension, heart failure, and atherosclerosis. Vascular endothelial growth factor is crucial for cardiac homeostasis as a critical molecule in cardiac angiogenesis. Neuronal nitric oxide synthase is an essential enzyme producing nitric oxide, a key regulator of vascular tone. The present study aims to shed light upon the complex interactions between these three vital signaling molecules and examine their changes with the progression of hypertensive heart disease. We used two groups of spontaneously hypertensive rats and age-matched Wistar rats as controls. The expression of the apelin receptor, vascular endothelial growth factor, and neuronal nitric oxide synthase were assessed immunohistochemically. We used capillary density and cross-sectional area of the cardiomyocytes as quantitative parameters of cardiac hypertrophy. Immunoreactivity of the molecules was more potent in both ventricles of spontaneously hypertensive rats compared with age-matched controls. However, capillary density was lower in both ventricles of the two age groups of spontaneously hypertensive rats compared with controls, and the difference was statistically significant. In addition, the cross-sectional area of the cardiomyocytes was higher in both ventricles of the two age groups of spontaneously hypertensive rats compared with controls, and the difference was statistically significant. Our study suggests a potential link between the apelin receptor, vascular endothelial growth factor, and neuronal nitric oxide synthase in cardiac homeostasis and the hypertensive myocardium. Nevertheless, further research is required to better comprehend these interactions and their potential therapeutic implications.

Are There Any Differences in the Healing Capacity between the Medial Collateral Ligament's (MCL) Proximal and Distal Parts in the Human Knee? Quantitative and Immunohistochemical Analysis of CD34, α-Smooth Muscle Actin (α-SMA), and Vascular Endothelial Growth Factor (VEGF) Expression Regarding the Epiligament (EL) Theory.

The human knee is a complex joint that comprises several ligaments, including the medial collateral ligament (MCL). The MCL provides stability to the knee and helps prevent its excessive inward movement. The MCL also has a thin layer of connective tissue known as the epiligament (EL), which adheres to the ligament. This unique feature has drawn attention in the field of ligament healing research, as it may have implications for the recovery process of MCL injuries. According to the EL theory, ligament regeneration relies heavily on the provision of cells, blood vessels, and molecules. The present study sought to compare the expression of vascular endothelial growth factor (VEGF), CD34, and α-smooth muscle actin (α-SMA) in healthy knees' proximal and distal MCL segments to better understand how these proteins affect ligament healing. By improving the EL theory, the current results could lead to more effective treatments for ligament injury. To conduct the present analysis, monoclonal antibodies were used against CD34, α-SMA, and VEGF to examine samples from 12 fresh knee joints' midsubstance MCLs. We identified a higher cell density in the EL than in the ligament connective tissue, with higher cell counts in the distal than in the proximal EL part. CD34 immunostaining was weak or absent in blood vessels and the EL, while α-SMA immunostaining was strongest in smooth muscle cells and the EL superficial layer. VEGF expression was mainly in the blood vessels' tunica media. The distal part showed more SMA-positive microscopy fields and higher cell density than the proximal part (4735 vs. 2680 cells/mm2). Our study identified CD34, α-SMA, and VEGF expression in the MCL EL, highlighting their critical role in ligament healing. Differences in α-SMA expression and cell numbers between the ligament's proximal and distal parts may explain different healing capacities, supporting the validity of the EL theory in ligament recovery.

Effect of leptin on nitrergic neurons in the lateral hypothalamic area and the supraoptic nucleus of rats.

The adipocyte-derived hormone, leptin, plays a key role in the maintenance of energy homeostasis. Leptin binds to the long form of its receptor, which is predominantly expressed in various hypothalamic regions, including the lateral hypothalamic area (LH) and supraoptic nucleus (SO). Several studies have suggested that leptin directly activates neuronal nitric oxide synthase, leading to increased nitric oxide production. We used histochemistry for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) as a marker for nitric oxide synthase activity and assessed the effect of leptin on nitrergic neurons in the LH and SO of rats. We found that intraperitoneal administration of leptin led to a significant increase in the number of NADPH-d-positive neurons in the LH and SO. In addition, the intensity (optical density) of NADPH-d staining in LH and SO neurons was significantly elevated in rats that received leptin compared with saline-treated rats. These findings suggest that nitrergic neurons in the LH and SO may be implicated in mediating the central effects of leptin.

The enigmatic os supratrochleare anterius: from rarity to recognition in elbow pathology-case report and review of literature.

Accessory bones around the elbow are scarce, with a reported mean incidence rate of 0.77%. The rarest one is the os supratrochleare anterius, with only a handful of documented cases in the literature. Despite their scarcity, various types of ossicles have been documented, posing diagnostic challenges and potential misinterpretation on X-rays. Herein, we report a case of an accidentally found os supratrochleare anterius in a 43-year-old pig farmer presenting with symptoms of tennis elbow. After conservative treatment with nonsteroidal anti-inflammatory drugs and physiotherapy, he made a full recovery within 2 weeks. This report emphasizes the rarity of the ossupra trochleare anterius, the importance of accurate diagnosis, and the need for continued research and awareness of this anatomical variation.

Do the Differences in the Epiligament of the Proximal and Distal Parts of the Anterior Cruciate Ligament Explain Their Different Healing Capacities? Quantitative and Immunohistochemical Analysis of CD34 and α-SMA Expression in Relation to the Epiligament Theory.

The aim of this study was to assess the epiligament theory by determining the normal epiligament morphology of the proximal and distal parts of the anterior cruciate ligament in humans and analyzing the differences between them and the midportion of the ligament in terms of cell numbers and expression of CD34 and α-SMA. Samples were obtained from the anterior cruciate ligaments of 12 fresh knee joints. Monoclonal antibodies against CD34 and α-SMA were used for immunohistochemistry. Photomicrographs were analyzed using ImageJ software, version 1.53f. The cell density was higher in the epiligament than in the ligament connective tissue. Cell counts were higher in the proximal and distal thirds than in the midsubstance of the epiligament. CD34 was expressed similarly in the proximal and distal thirds, although it seemed slightly more pronounced in the distal third. α-SMA expression was more robust in the proximal than the distal part. The results revealed that CD34 and α-SMA are expressed in the human epiligament. The differences between the numbers of cells in the proximal and distal parts of the epiligament and the expression of CD34 and α-SMA enhance epiligament theory. Future investigations into improving the quality of ligament healing should not overlook the epiligament theory.

A Rare Case of Thyroidea Ima Arising From the Internal Thoracic Artery and Reaching Up to the Parathyroid Gland.

The thyroidea ima artery (TIA), also known as the Neubauer artery, is a variable artery that takes part in the blood supply of the thyroid gland. The overall prevalence rate of the thyroidea ima artery is 3.3%. Though it most commonly branches off the brachiocephalic trunk or the arch of the aorta, the artery has a highly variable origin point. Herein, we present a rare case of a thyroidea ima originating from the left internal thoracic artery, found during routine dissection of a Caucasian, 76-year-old, male, formalin-fixed cadaver. The artery is a normal finding during embryological development as a part of a more extensive network of vessels supplying the thyroid gland. The latter undergoes significant remodeling, and only four superior and inferior thyroid arteries remain. Thus, the presence of the thyroidea ima is considered to be due to changes in the said remodeling process. Due to its course, anteriorly to the trachea, the thyroidea ima artery might pose problems during different surgical procedures regarding the inner anterior region of the neck, such as tracheotomy, thyroidectomy, laryngeal transplantation, and selective embolization of the thyroid arteries (SETA). Furthermore, complications during the operative treatment of parathyroid conditions and mediastinal bleeding are to be expected. The variable presence and origin of the thyroidea ima have clear and significant clinical and surgical implications. They must be considered when procedures in the neck's anterior region occur.

A Case-Control Study of the Fokl Polymorphism of the Vitamin D Receptor Gene in Bulgarians With Lumbar Disc Herniation.

BACKGROUND: The present study investigates whether vitamin D receptor (VDR) gene polymorphisms play a role in intervertebral disc degeneration (IDD), a common cause of low back pain (LBP) and reduced quality of life. Specifically, we examined the FokI VDR polymorphism and its potential association with lumbar disc herniation (LDH) in patients from Bulgaria. Previous studies have suggested a link between mutations in the VDR gene and IDD. METHODS: We investigated whether a potential connection between VDR polymorphisms and LDH was present by comparing the FokI polymorphism of 60 selected patients (25 to 60) with LDH and 60 healthy volunteers within the same age range. We used polymerase chain reaction to assess the phenotype of the examined subjects and statistical tests to evaluate whether the obtained results were statistically significant. RESULTS: The performed genetic and statistical analyses reviewed significant differences in genotypic frequencies between the patient group and healthy volunteers. The frequency of the F allele is notably higher in patients with LDH (80%) compared to volunteers (52%), while the f allele is more common among patients (86.6%) than volunteers (100%). CONCLUSION: This study strongly suggests that expression of the F allele of the VDR gene may increase the susceptibility of developing LDH, while having the f allele could potentially have a protective effect. Our results shed light on the underlying complex mechanisms contributing to the development of LDH.

A Rare Variation of the Levator Scapulae Muscle: A Case Report and Review of Literature.

Muscle variations in the posterior neck region are mainly categorized as variations in the origin and insertion of the muscles and the presence of accessory slips or rudimentary muscles. The levator scapulae muscle is a variable muscle with several different types of variations described throughout the literature. Herein, we report a rare unilateral case of an accessory slip from the levator scapulae. Aberrant muscle slip originates from the distal one-third of the levator scapulae. Then, it passes upwards and outwards above a vascular bundle containing a superficial branch of the transverse cervical artery and vein. The deviant muscle slip inserts onto the superior nuchal line. Muscle variations in the neck's posterior region and the levator scapulae's variations, as per se, have the utmost clinical significance since they might be mistaken for tumor mass. Moreover, such variations might be deceptive during surgical procedures in the region. Therefore, detailed knowledge of such complex muscular variations in the posterior region of the neck is paramount for surgeons and radiologists alike.

Disorder of sexual development, urinary bladder duplication, pancake kidney and neural tube defect.

Congenital malformations of the urogenital system with fully developed duplications, such as urinary bladder, are sporadic. They are often present in the setting of endogenous molecular disbalance, such as steroid metabolism disturbances. Other rare manifestations of hormonal disbalance present as intersex conditions in which the individual has karyotype-specific internal genital organs with opposite-sex signs of the external genitalia, known as ambiguous genitalia. Congenital variations and malformations are often fully recognized and understood during radiological exams. Herein we present a unique case of a 2-month-old baby with female chromosomal sex and ambiguous genitalia together with the manifestation of several anatomical malformations: urinary bladder duplication in the coronal plane, pancake kidney with supernumerary renal arteries, 2 ureters and neural tube defect. Despite their low incidence rate, knowledge of such malformations is paramount for correct diagnosis and treatment in such cases.

New insight into the morphological characteristics of patella cubiti.

Accessory bones in the elbow region are rare anatomical variations with important clinical significance as they can be misdiagnosed as pathological lesions. Usually, they are asymptomatic and found incidentally during X-ray examination in the context of trauma. Although these bones have been previously described, their development is not fully understood. The present case provides complex macroscopic, X-ray and histological descriptions of a sesamoid bone in the posterior region of the elbow-patella cubiti and the related surrounding structures. Moreover, this report indicates the presence of a well-defined syndesmosis between patella cubiti and the proximal ulna.

Microcirculatory changes as a hallmark of aging in the heart and kidney / Cambios microcirculatorios como sello distintivo del envejecimiento en el corazón y riñón

SUMMARY: Changes in the microcirculation of multiple tissues and organs have been implicated as a possible mechanism in physiological aging. In particular, vascular endothelial growth factor is a secretory protein responsible for regulating angiogenesis via altering endothelial proliferation, survival, migration, extracellular matrix degradation and cell permeability. The aim of the present study was to evaluate the role of vascular endothelial growth factor in the progression of morphological alterations caused by physiological aging in the heart and kidney and to examine its relation to changes in capillary density. We used two age groups of healthy Wistar rats - 6- and 12-month- old. The expression of vascular endothelial growth factor was examined through immunohistochemistry and immunofluorescence and assessed semi-quantitatively. Changes in capillary density were evaluated statistically and correlated with the expression of vascular endothelial growth factor. We reported stronger immunoreactivity for vascular endothelial growth factor in the left compared to the right ventricle and also observed an increase in its expression in both ventricles in older animals. Contrasting results were reported for the renal cortex and medulla. Capillary density decreased statistically in all examined structures as aging progressed. The studied correlations were statistically significant in the two ventricles in 12-month-old animals and in the renal cortex of both age groups. Our results shed light on some changes in the microcirculation that take place as aging advances and likely contribute to impairment in the function of the examined organs.

Los cambios en la microcirculación de múltiples tejidos y órganos se han implicado como un posible mecanismo en el envejecimiento fisiológico. En particular, el factor de crecimiento endotelial vascular es una proteína secretora responsable de regular la angiogénesis mediante la alteración de la proliferación endotelial, la supervivencia, la migración, la degradación de la matriz extracelular y la permeabilidad celular. El objetivo del presente estudio fue evaluar el papel del factor de crecimiento del endotelio vascular en la progresión de las alteraciones morfológicas causadas por el envejecimiento fisiológico en el corazón y riñón y examinar su relación con los cambios en la densidad capilar. Utilizamos dos grupos de ratas Wistar sanas: 6 y 12 meses de edad. La expresión del factor de crecimiento del endotelio vascular se examinó mediante inmunohistoquímica e inmunofluorescencia y se evaluó semicuantitativamente. Los cambios en la densidad capilar se evaluaron estadísticamente y se correlacionaron con la expresión del factor de crecimiento del endotelio vascular. Informamos una inmunorreactividad más fuerte para el factor de crecimiento endotelial vascular en el ventrículo izquierdo en comparación con el derecho y también observamos un aumento en su expresión en ambos ventrículos en animales mayores. Se informaron resultados contrastantes para la corteza renal y la médula. La densidad capilar disminuyó estadísticamente en todas las estructuras examinadas a medida que avanzaba el envejecimiento. Las correlaciones estudiadas fueron estadísticamente significativas en los dos ventrículos en animales de 12 meses y en la corteza renal de ambos grupos de edad. Nuestros resultados arrojan luz sobre algunos cambios en la microcirculación que tienen lugar a medida que avanza el envejecimiento y probablemente contribuyan a un deterioro en la función de los órganos examinados.

Variant origin of the right coronary artery from the left main coronary artery together with aortic valve stenosis: report of a rare case / Origen variante de la arteria coronaria derecha a partir de la arteria coronaria izquierda junto con estenosis de la valva aórtica: reporte de un caso raro

SUMMARY: Variations in the origin of the right coronary artery have an incidence between 0.09 % and 0.92 %. Herein, we report a rare case of a coronary artery anomaly in which the right coronary artery originates from the left main coronary artery. This variant was found during routine coronarography, combined with an artificial aortic valve. Despite their rare occurrence, some variations in the origins of the coronary arteries can be life threatening and are associated with a higher risk of sudden cardiac death. They can also pose serious technical challenges and predispose to complications during coronary angiographic procedures. Thus, knowledge of such anomalies is paramount for managing the patients correctly.

Las variaciones en el origen de la arteria coronaria derecha tienen una incidencia entre el 0,09 % y el 0,92 %. En este documento, informamos un caso raro de una anomalía de la arteria coronaria en la que la arteria coronaria derecha se originaba en la arteria coronaria izquierda. Esta variante se encontró durante una coronariografía de rutina, combinada con una válvula aórtica artificial. A pesar de su rara aparición, algunas variaciones en los orígenes de las arterias coronarias pueden poner en peligro la vida y se asocian con un mayor riesgo de muerte súbita cardíaca. También pueden plantear serios desafíos técnicos y predisponer a complicaciones durante los procedimientos angiográficos coronarios. Por tanto, el conocimiento de dichas anomalías es fundamental para el manejo correcto de los pacientes.

Patella cubiti - a continuing etiological mystery / Patella cubiti: un misterio etiológico continuo

SUMMARY: A sesamoid bone in the elbow joint is a rare anatomical variation described as a Patella cubiti. Although this variation has been known for centuries its exact etiology is still unclear. Congenital, developmental, and traumatic hypotheses have been proposed. It seldom causes clinical manifestations than elbow stiffness or hypomobility. Herein, we present a case of a 31-year-old patient admitted to our department with complaints of swelling and erythema in the right elbow. An X-ray image revealed a triangular accessory bone with rounded edges, which was diagnosed as a Patella cubiti in combination with olecranon bursitis. Knowledge of this rare elbow abnormality is paramount for orthopedic surgeons and roentgenologists in their daily medical practice.

Un hueso sesamoideo en la articulación del codo es una rara variación anatómica descrita como Patella cubiti. Aunque esta variación se conoce desde hace siglos, su etiología exacta aún no está clara. Se han propuesto hipótesis congénitas, de desarrollo y traumáticas. Rara vez causa manifestaciones clínicas que no sean rigidez o hipomovilidad del codo. Presentamos el caso de un paciente de 31 años que ingresó en nuestro servicio por presentar tumefacción y eritema en el codo derecho. Una imagen de rayos X reveló un hueso accesorio triangular con márgenes redondeados, que se diagnosticó como una Patella cubiti en combinación con bursitis del olécranon. El conocimiento de esta rara anomalía del codo es fundamental para los cirujanos ortopédicos y los médicos radiólogos en su práctica médica diaria.

Depletion of vascular adaptive mechanisms in hypertension-induced injury of the heart and kidney.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a signalling protein of critical importance for angiogenesis. In an effort to better understand its significance in hypertension-induced injury of the heart and kidney we aimed at studying the changes in its expression in an experimental model and correlated it with capillary density in the myocardium and the renal parenchyma. METHODS: We used two age groups of spontaneously hypertensive rats (6- and 12-month-old), indicative of early and advanced hypertension. VEGF expression was assessed and a semi-quantitative analysis of its immunoreactivity was conducted. Changes in capillary density in the myocardium and kidney were assessed for statistical significance and correlations with VEGF expression were established. RESULTS: We reported stronger VEGF expression in animals with early compared to advanced hypertension in all examined structures. Capillary density decreased significantly at age 12 months compared to 6 months and was significant in all examined structures. A positive correlation was established between capillary density and the expression of VEGF. CONCLUSION: These findings underscore the key significance of VEGF for compensatory angiogenesis and suggest that a statistically significant depletion of these vascular adaptive mechanisms is a major aspect in the cascade of hypertension-induced injury of the heart and kidney (Tab. 3, Fig. 26, Ref. 47).

A comparative study of the epiligament of the medial collateral and anterior cruciate ligaments in the human knee: Immunohistochemical analysis of CD 34, α-smooth muscle actin and vascular endothelial growth factor in relation to epiligament theory.

BACKGROUND: This study evaluated and compared the expression of VEGF, CD34, and α-SMA in the anterior cruciate ligaments and medial collateral ligaments in healthy human knees in order to enrich the epiligament theory regarding ligament healing after injury. METHODS: Samples from the mid-substance of the anterior cruciate ligament and the medial collateral ligament of 12 fresh knee joints were used. Monoclonal antibodies against CD34, α-SMA, and VEGF were used for immunohistochemical analysis. Photomicrographs were analyzed using the ImageJ software. RESULTS: The epiligament of the anterior cruciate ligament showed slightly higher expression of CD34, α-SMA, and VEGF than the epiligament of the medial collateral ligament. Overall, among the tested markers, α-SMA expression was most pronounced in anterior cruciate ligament epiligament images and CD34 dominated in medial collateral ligament epiligament images. The intensity of DAB staining for CD34, α-SMA, and VEGF was higher in vascular areas of the epiligament than in epiligament connective tissue. CONCLUSIONS: The results illustrate that CD34, α-SMA, and VEGF are expressed in the human epiligament. The differences between the epiligament of the investigated ligaments and the fact that CD34, α-SMA, and VEGF, which are known to have a definite role in ligament healing, are predominantly expressed in the main vascular part of the ligament-epiligament complex enlarge the existing epiligament theory. Future investigations regarding better ligament healing should not overlook the epiligament tissue.

Mast cells and basic fibroblast growth factor in physiological aging of rat heart and kidney.

Age-related morphological and physiological changes occur in cells, tissues and organs with high metabolic or mitotic activity; these changes decrease their regenerative capacity. One such change is interstitial fibrosis. Mast cells contain basic fibroblast growth factor and have been related to pro-fibrotic activity. We investigated the role of mast cells in physiological aging of the heart and kidney. We analyzed changes in mast cell number and compared the left and right heart ventricles and kidneys of 6- and 12-month-old Wistar rats. We also evaluated the immunohistochemical expression of basic fibroblast growth factor. Finally, we analyzed changes in the extent of interstitial fibrosis and in the glomerular sclerosis index as nonspecific markers of aging and correlated these parameters with of mast cells. Mast cells were visualized by toluidine blue staining and specific immunohistochemical expression of tryptase. The expression of basic fibroblast growth factor was assessed semiquantitatively. The extent of interstitial fibrosis was investigated using Mallory's trichrome staining. Glomerular sclerosis was evaluated using periodic acid-Schiff staining. We found that the number of mast cells increased significantly in the older rats. We also found that the number of mast cells was greatest in the left ventricle followed by the right ventricle, then the kidney. The immunoreactivity of basic fibroblast growth factor also increased in older animals. Correlations between the number of mast cells and immunoreactivity of basic fibroblast growth factor, extent of interstitial fibrosis and glomerular sclerosis index demonstrated the association between mast cells and age-related tissue remodeling of the heart and kidney.

The novel epiligament theory: differences in healing failure between the medial collateral and anterior cruciate ligaments.

According to current literature, 90% of knee ligament injuries involve the medial collateral ligament or the anterior cruciate ligament. In contrast to the medial collateral ligament, which regenerates relatively well, the anterior cruciate ligament demonstrates compromised healing. In the past, there were numerous studies in animal models that examined the healing process of these ligaments, and different explanations were established. Although the healing of these ligaments has been largely investigated and different theories exist, unanswered questions persist.Therefore, the aim of this article is 1) to review the different historical aspects of healing of the medial collateral ligament and present the theories for healing failure of the anterior cruciate ligament; 2) to examine the novel epiligament theory explaining the medial collateral ligament healing process and failure of anterior cruciate ligament healing; and 3) to discuss why the enveloping tissue microstructure of the aforementioned ligaments needs to be examined in future studies.We believe that knowledge of the novel epiligament theory will lead to a better understanding of the normal healing process for implementing optimal treatments, as well as a more holistic explanation for anterior cruciate ligament healing failure.

Neuroprotective effect of newly synthesized 4-aminopyridine derivatives on cuprizone-induced demyelination in mice-a behavioral and immunohistochemical study.

The aim of this study was to assess the effect of newly synthesized derivatives of 4-aminopyridine (4-AP) on cuprizone-induced model of brain demyelination in mice. 4-AP is already approved for the treatment of walking difficulties in patients with multiple sclerosis. The model of demyelination was carried out by the administration of cuprizone to the drinking water of the experimental mice. Besides cuprizone, 4-AP derivatives and 4-AP were administered to the groups in order to assess their protective effect on the demyelination. We used immunohistochemistry for visualization of changes in corpus callosum. Memory storage processes were also assessed with the passive avoidance test on the last two days of the experiment. The experimental mice treated with compounds 4b and 4c increased significantly their latency time on the second day in comparison to the control group which indicated an improved memory process. The number of mature oligodendrocytes in the groups treated with compounds 4b, 4c and 4-AP is closer to those in the control group. The results of our studies showed that the newly synthesized compounds 4b and 4c reverse the effect of cuprizone. These groups also showed increased latency time in the passive avoidance test in comparison to the control group.