Effect of prolonged administration of bovine lactoferrin in neuropathic pain: involvement of opioid receptors, nitric oxide and TNF-alpha.

AIMS: This study aimed to investigate the effect of prolonged administration of bovine milk lactoferrin (bLF) on hyperalgesia and allodynia in a rat model of neuropathic pain and to determine the involvement of c-Fos, TNF-alpha, nitric oxide and opioidergic systems in this effect. MAIN METHODS: Neuropathic pain was induced in rats by loose ligation of the right sciatic nerve and evaluated by tests measuring the mechanical and thermal hyperalgesia and allodynia. bLF (50, 100, and 200mg/kg) alone or in combination with opioidergic antagonists were administered intraperitoneally to the rats with neuropathic pain. c-Fos and NADPH-d immunocytochemistry and Western blotting for TNF-alpha, iNOS and nNOS were performed in the lumbar spinal cord of rats. Plasma TNF-alpha levels were determined with ELISA. KEY FINDINGS: Prolonged, but not single, administration of bLF produced antihyperalgesic and antiallodynic effects in neuropathic rats. Pretreatment with opioidergic antagonists significantly decreased this effect. Prolonged administration of bLF decreased c-Fos and NADPH-d immunoreactivity and TNF-alpha and iNOS expressions at 50 and 100mg/kg and nNOS expression at 100mg/kg in the lumbar spinal cord of neuropathic rats. Plasma TNF-alpha levels remained unchanged after bLF treatment. SIGNIFICANCE: Prolonged administration of bLF exerts antihyperalgesic and antiallodynic effect in neuropathic rats; down-regulation of both TNF-alpha and iNOS expressions and potentiation of opioidergic system in the lumbar spinal cord can contribute to this effect.

Morphology and innervation of the human cremaster muscle in relation to its function.

The electromyographic properties of the cremaster muscle (CM) are quite different from other skeletal muscles. It shows excessive spontaneous discharges, and the motor unit shape and firing frequency of the CM muscle differ from that of limb muscles. In this study, CM of six adult cadavers and six orchiectomy specimens were used to reveal the detailed histology of the muscle and provide an anatomophysiological explanation for these unusual electromyographic properties. Routine histochemical stains revealed the CM was composed of several distinct bundles of smooth and striated muscle fibers within connective tissue. The smooth muscle fibers that were more profuse than previously known and were not arranged in layers, but widely dispersed between striated muscle fibers. Bielschowsky silver staining technique, anti-neurofilament and anti-synaptophysin immunostaining showed the presence of multiple motor end-plates observed as a series of small dots or lines running along the striated muscle fibers and several nerve endings on a single muscle fiber. Myosin immunostaining confirmed the CM is a slow-twitch muscle, and alpha-actin smooth muscle immunostaining confirmed the presence of a large number of smooth muscle fibers. There were also small multipolar neurons forming nerve plexuses between smooth muscle fibers. Anti-GFAP immunostaining confirmed the presence of glial cells similar to astrocytes. In conclusion, the findings of this detailed anatomical study showed the CM, widely known as a striated muscle, contains a large number of smooth muscle fibers, and the spontaneous electromyographic discharges are due to the presence of multiple motor end-plates and dense innervation.

Nicotinamide adenine dinucleotide phosphate-diaphorase and c-fos expression in spinal cord neurons following noxious stimulation.

OBJECTIVE: To investigate nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and fos expression in spinal cord dorsal horn neurons following noxious peripheral stimulation. METHODS: Expression of the immediate-early gene c-fos and nitric oxide containing neurons one hour after unilateral formalin injection to the dorsal hind paw was investigated in rat lumbar spinal cord, using fos immunohistochemistry and NADPH-d histochemical techniques. The experiments were performed in 2004 and 2006 at Ege University Center for Brain Research in Izmir, Turkey. RESULTS: In 10 adult male Sprague-Dawley rats, an increase in fos-immunoreactive neurons was observed ipsilateral, and NADPH-d positive neurons equally ipsi- and contralateral to the formalin injection site. Approximately 20% of fos-immunoreactive neurons were NADPH-d positive ipsilateral to the formalin injection, whereas no double labeling was observed in the contralateral side. Also, a close relation of NADPH-d positive processes with fos-immunoreactive nuclei were also observed. CONCLUSION: The results of this study support the hypothesis that nitric oxide synthase blocking agents may serve as a possible alternative in treatment of hyperalgesia following inflammation and peripheral nerve injury.

Morphometry of the cervical vertebral pedicles as a guide for transpedicular screw fixation.

Anatomical measurements of the cervical pedicle in a large series of human cervical vertebrae from 48 individuals were obtained to reduce the incidence and severity of complications caused by transpedicular screw placement. The greatest pedicle length was at C-3 and the greatest pedicle width was at C-6. Pedicle width and lateral mass thickness gradually increased from C-3 to C-6. Pedicle height and interpedicular distance increased from C-3 to C-5, and decreased slightly at C-6. The lateral mass-pedicle length was greatest at C-4. The present study found right-left differences for the pedicle-spinous process distance at C-6 (p < 0.05). Pedicle width and height were smaller than those reported in earlier studies, especially at C-3 and C-4, whereas the increasing pedicle widths at C-5 and C-6 were appropriate for pedicle screw fixation.

Incidence and morphology of the accessory head of the flexor pollicis longus muscle (Gantzer`s muscle) in a Turkish population.

OBJECTIVE: To present the incidence, morphology, and the relationships of the accessory head of the flexor pollicis longus (Gantzer`s) muscle (AHFPL) in a recent Turkish population. METHODS: The study was performed on 52 upper extremities of 26 adult Turkish cadavers in the Department of Anatomy, Ege University Faculty of Medicine, Izmir, Turkey in 2005. In our dissections, the prevalence and anatomical morphology of the AHFPL including muscle shape, origin and insertion point, and its relation to the anterior interosseous nerve (AIN) was examined. RESULTS: The AHFPL muscle was found in 27 upper extremities (51.9%). It was bilateral in 10 cadavers (74%), and unilateral in 7 cadavers (26%). The muscle shape was spindle in 19 (70.4%), and papillary in 8 (29.6%). The AHFPL originated from the coronoid process of the ulna in 22 upper extremities (81.5%), and the medial epicondyle of the humerus in 5 cases (18.5%). The AIN passed anterior to the AHFPL in one case (3.7%), lateral in 3 (11.1%), posterolateral in 8 (29.6%) and posterior in 15 (55.6%) cases. CONCLUSION: The knowledge of the morphology and the topography of the AIN and AHFPL is important for understanding the mechanism of the AIN syndrome. The results of this study show the mechanical compression due to the AHFPL may be a cause of the pronator and AIN syndromes.

Topographic anatomy of the fornix as a guide for the transcallosal-interforniceal approach with a special emphasis on sex differences.

The topographic anatomy and morphometry of the fornix is important for standardizing the transcallosal-interforniceal approach and avoiding memory disturbances. The detailed morphometry of the fornix was investigated with a special emphasis on sex differences using midsagittal magnetic resonance imaging of 80 males and 102 females. Various parameters of the fornix, including the length of the upper and lower fornices, the curvature of the upper and lower fornices, and the insertion point of the fornix to corpus callosum, were investigated. The thickness of the fornix at the attachment point to the anterior commissure, the maximum distance to the upper and lower surfaces of the fornix, and the curvature of the upper and lower fornices showed sex differences (p < 0.5). The upper insertion point of the fornix to the corpus callosum was more frontal in females, but the functional relevance of these differences need further investigation.

Variations in sphenoid sinus anatomy with special emphasis on pneumatization and endoscopic anatomic distances.

OBJECTIVE: The purpose of this study was to present the morphometry and pneumatization of the sphenoid sinus in detail for the neurosurgeon for transnasal approach to the hypophyseal tumors and especially for functional endoscopic sinus surgery. METHODS: One hundred and eighty midsagittal magnetic resonance images, 48 bones and 29 hemi-sectioned cadaveric heads obtained from Ege University, Faculty of Medicine, Departments of Anatomy and Radiology were used in 2003. The sphenoid sinuses were classified into sellar, pre-sellar, conchal and post-sellar types according to the extent of their posterior limits. Different measurements based on the surgical approach and sinus size were performed. RESULTS: Conchal type sinus was observed in 1.9%, pre-sellar type 9%, sellar type 52.9% and post-sellar type 36.2% of the specimens. Conchal type sphenoid sinus was not observed in males, but in 1.7% of females. Pre-sellar type was observed in 5.6% of males and 2.8% of females. Sellar type was found in 24.4% of males and 23.9% females, and post-sellar type in 19.5% of males and 22.2% of females. The sphenoid sinus length at the upper and lower parts was 13.51+/-3.25mm and 24.57+/-6.65mm. The sphenoid sinus height at the anterior and posterior parts was 21.27+/-4.25mm and 14.5+/-4.07mm. Distance from the ostium to limen was 56.6+/-5.6mm and from ostium to sill was 64.6+/-6.11mm in cadaveric specimens. In MR images, distance from the ostium to the sill was 68.7+/-5.9mm and from sella to sill 82.8+/-6.2mm. CONCLUSION: Sphenoid sinus variations observed in pneumatization, size, localization and shape are important in providing a better surgical approach and avoiding surgical complications.

Morphometry of the anterior third ventricle region as a guide for the transcallosal-interforniceal approach.

The transcallosal-interforniceal approach is the most appropriate approach to localize and totally remove space-occupying lesions around the anterior third ventricle region such as craniopharyngiomas and gliomas. This study examined the microsurgical anatomy of the normal anterior third ventricle region in 81 adult cadaver hemispheres. The central sulcus was identified and surface landmarks determined as the points 5 cm (P5) and 7 cm anterior to the central sulcus (P7). The distances between P5 and P7 and the upper margin of the interventricular foramen, which delineate the surgical corridor chosen to avoid disturbance of important neural structures, were 46.26-60.96 (54.09 +/- 3.35) mm and 48.00-62.00 (54.94 +/- 3.09) mm, respectively. The distances between the upper margin of the hemisphere and the cingulate sulcus, especially important for avoiding damage to the cingulate gyrus and other mesiolimbic structures, were 13.54-30.00 (21.28 +/- 3.89) mm and 12.22-29.52 (21.12 +/- 3.90) mm at the level of P5 and P7. The distances between the upper margin of the hemisphere and the callosal cistern containing the pericallosal artery were 28.34-40.50 (33.94 +/- 2.84) mm and 28.16-40.26 (33.50 +/- 2.61) mm, respectively. Normative morphometric data of the structures involved in the surgical procedure are necessary for planning and performance of the transcallosal-interforniceal approaches. This study of a large series of specimens shows that these measurements have large individual variations.

Expression of c-Fos and NADPH-d after peripheral noxious stimulation in the pedunculopontine tegmental nucleus.

The participation of pedunculopontine tegmental nucleus in descending pain control mechanisms has been proposed. The aim of this study was to investigate NADPH-d and c-Fos reactivity in the pedunculopontine tegmental nucleus following noxious peripheral stimulation. Formalin induced hind paw inflammation in the rat resulted in bilateral increase of Fos and NADPH-d expression in the pedunculopontine tegmental nucleus. Approximately 30% of labelled cells were double-labelled. Close proximity to NADPH-d labelled neuronal processes with Fos-labelled nuclei were observed. This anatomical relationship supports the hypothesis that pedunculopontine tegmental nucleus is involved in pain modulation and proposes a new explanation for the presence of nitric oxide in this nucleus.

Heights of the cerebral falx. Surgical and clinical implications.

OBJECTIVE: Variations in the shape and size of the cerebral falx can embarrass the surgical treatment of lesions in and around the falx. In this study, anatomy and morphometry of the cerebral falx in adult cadaveric specimens were examined to enable easy approach during surgery. METHODS: Fifty-two adult cadaver cerebral hemispheres with dura from the cadaver collection of the Department of Anatomy, Ege University, Faculty of Medicine were examined in 2003. The cerebral falx was observed in 3 different types. The heights of the cerebral falx and the heights of interspace between the lower margin of the cerebral falx and corpus callosum were measured. RESULTS: The most frequently observed type of cerebral falx was Type I based on the classification of Jiang and Jia. The average heights of the cerebral falx measured 21.3 mm anteriorly, 25.7 mm in the middle and 45.6 mm posteriorly in Type I; 27.9 mm anteriorly, 30.5 mm in the middle and 47 mm posteriorly in Type II; 28.7 mm anteriorly, 36.5 mm in the middle and 44.1 mm posteriorly in Type III. The average heights of the interspace between the lower margin of the cerebral falx and corpus callosum were 14.1 mm anteriorly, 12.4 mm in the middle and 2.1 mm posteriorly in Type I; 6.3 mm anteriorly, 7.2 mm in the middle and 1 mm posteriorly in Type II; 2.3 mm anteriorly, 1.8 mm in the middle and 0.6 mm posteriorly in Type III. Natural defects were found on the cerebral falx in 12 (23%) specimens. CONCLUSION: Measurements of the cerebral falx provide useful information for neurosurgeons in treatment of lesions involving the region. This study presents more detailed data compared to those reported in the few previously published papers, results differing due to differences of the populations investigated.

Anatomy of the clinoidal region with special emphasis on the caroticoclinoid foramen and interclinoid osseous bridge in a recent Turkish population.

In this study we present the incidence of caroticoclinoid foramen and interclinoid osseous bridge and some topographic aspects regarding the clinoidal internal carotid artery (ICA) in a recent Turkish population to provide a guide for neurosurgeons in any surgical approach, especially to the cavernous sinus. One hundred nineteen adult dry skulls and 52 adult cadaveric heads were used for this purpose. Caroticoclinoid foramen and the interclinoid osseous bridge were divided into three types based on the classification of Keyers [13]. Caroticoclinoid foramen was observed in 35.67% of the specimens, unilaterally in 23.98%, and bilaterally in 11.69%. The complete-type caroticoclinoid foramen was observed in 4.09% of the specimens, the contact type in 4.68%, and the incomplete type in 14.91%. Transverse diameter of the foramen was 5.32+/-0.52 mm for the incomplete type. The incidence of interclinoid osseous bridge was 8.18%. The middle clinoid process was prominent in 15.12% of cases and rudimental in 13.23%. The mean distance between the proximal and distal dural rings of the clinoidal ICA was 4.51+/-0.44 mm, and mean diameter of the distal ring was 5.25+/-0.59 mm. Right-left differences were assessed for each parameter, and populational differences are discussed.

Morphometry of the anterior third ventricle region as a guide for the subfrontal (translaminaterminalis) approach.

The anterior third ventricle region acquires clinical significance in benign and malignant tumors and cyst formations, of which craniopharyngiomas and gliomas are the most common. The subfrontal approach is one of the most preferred approaches for removing these tumors. In this study, the microsurgical anatomy of 81 Turkish, adult cadaveric hemispheres was examined to provide morphometric data of the region. These measurements from the anterior third ventricle region serve as a guide for neurosurgeons during surgical approach for removing anterior third ventricle tumors.