Intraoperative imaging techniques in the treatment of brain tumors.

Despite significant advances in medical imaging techniques and their routine preoperative use, real-time intraoperative information regarding anatomy remains of indisputable importance to neurosurgeons. Intraoperative displacement of the brain tissue caused by surgical retraction or the resection cavity itself, as well as shift caused by cerebrospinal fluid leakage, may result in alteration of the surgical anatomy of the lesion and surrounding structures. Neurosurgical navigation methods are beneficial in providing accurate intraoperative information regarding the anatomy of the surgical field. Furthermore, interactive image guidance may decrease incision lengths, operating times, and postoperative morbidity. This review focuses on recent developments in neurosurgical navigational techniques that enable real-time anatomic visualization during brain tumor surgery.

Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury.

Heme oxygenase (HO) catalyzes the conversion of heme to carbon monoxide, iron, and biliverdin, which is immediately reduced to bilirubin (BR). Two HO active isozymes exist: HO1, an inducible heat shock protein, and HO2, which is constitutive and highly concentrated in neurons. We demonstrate a neuroprotective role for BR formed from HO2. Neurotoxicity elicited by hydrogen peroxide in hippocampal and cortical neuronal cultures is prevented by the phorbol ester, phorbol 12-myristate 13-acetate (PMA) via stimulation of protein kinase C. We observe phosphorylation of HO2 through the protein kinase C pathway with enhancement of HO2 catalytic activity and accumulation of BR in neuronal cultures. The neuroprotective effects of PMA are prevented by the HO inhibitor tin protoporphyrin IX and in cultures from mice with deletion of HO2 gene. Moreover, BR, an antioxidant, is neuroprotective at nanomolar concentrations.

Nitric oxide and carbon monoxide: parallel roles as neural messengers.

Nitric oxide is now appreciated to be a molecule with important signaling functions in the body. The purification and cloning of the first NO synthesizing enzyme, NO synthase (NOS), from brain has led to the characterization of the roles of NO in normal physiology and in pathogenic states. NO synthesis is regulated in a complex manner, involving the association of activatory and inhibitory proteins. The body appears to use at least one other, highly related gas in a signaling function, carbon monoxide (CO). The enzyme responsible for CO biosynthesis in brain, heme oxygenase-2 (HO2), is rapidly regulated by neurotransmitter stimulation. The role for CO as neurotransmitter is suggested by the altered intestinal motility in mice harboring a genomic deletion of HO2.

Targeted gene deletion of heme oxygenase 2 reveals neural role for carbon monoxide.

Neuronal nitric oxide synthase (nNOS) generates NO in neurons, and heme-oxygenase-2 (HO-2) synthesizes carbon monoxide (CO). We have evaluated the roles of NO and CO in intestinal neurotransmission using mice with targeted deletions of nNOS or HO-2. Immunohistochemical analysis demonstrated colocalization of nNOS and HO-2 in myenteric ganglia. Nonadrenergic noncholinergic relaxation and cyclic guanosine 3',5' monophosphate elevations evoked by electrical field stimulation were diminished markedly in both nNOSDelta/Delta and HO-2(Delta)/Delta mice. In wild-type mice, NOS inhibitors and HO inhibitors partially inhibited nonadrenergic noncholinergic relaxation. In nNOSDelta/Delta animals, NOS inhibitors selectively lost their efficacy, and HO inhibitors were inactive in HO-2(Delta)/Delta animals.

Heme oxygenase 2: endothelial and neuronal localization and role in endothelium-dependent relaxation.

Heme oxygenase 2 (HO-2), which synthesizes carbon monoxide (CO), has been localized by immunohistochemistry to endothelial cells and adventitial nerves of blood vessels. HO-2 is also localized to neurons in autonomic ganglia, including the petrosal, superior cervical, and nodose ganglia, as well as ganglia in the myenteric plexus of the intestine. Enzyme studies demonstrated that tin protoporphyrin-9 is a selective inhibitor of HO with approximately 10-fold selectivity for HO over endothelial nitric oxide synthase (NOS) and soluble guanylyl cyclase. Inhibition of HO activity by tin protoporphyrin 9 reverses the component of endothelial-derived relaxation of porcine distal pulmonary arteries not reversed by an inhibitor of NOS. Thus, CO, like NO, may have endothelial-derived relaxing activity. The similarity of NOS and HO-2 localizations and functions in blood vessels and the autonomic nervous system implies complementary and possibly coordinated physiologic roles for these two mediators.

Mutations in the Caenorhabditis elegans beta-tubulin gene mec-7: effects on microtubule assembly and stability and on tubulin autoregulation.

We have sequenced 45 mutations in mec-7, a beta-tubulin gene required for the production of 15-protofilament microtubules in the nematode Caenorhabditis elegans, and have correlated sequence alterations with mutant phenotypes. The expression patterns of most alleles have also been determined by in situ hybridization and immunocytochemistry. Most (12/16) complete loss-of-function alleles, which are recessive, result from nonsense mutations, insertions, or deletions; three others disrupt a putative GTP-binding domain. Three of the four loss-of-function, missense mutations result in elevated mec-7 message levels, suggesting a defect in tubulin autoregulation that may be attributable to a loss in the ability to form heterodimers. Most (8/9) mild alleles are caused by missense mutations. Two mild alleles appear to increase microtubule stability and lead to the elaboration of ectopic neuronal processes in mec-7-expressing cells. Most (15/23) mutations that cause severe dominant or semidominant phenotypes are clustered into three discrete domains; four others occur in putative GTP-binding regions. Many of these dominant mutations appear to completely disrupt microtubule assembly.

Arterial supply of the human endolymphatic duct and sac.

The arterial anatomy of the endolymphatic duct and sac was studied in vascular casts of methyl methacrylate of six human heads. The chief source of arterial blood supply to the endolymphatic duct and sac appeared to be the occipital artery. Arterioles entered the bone of the mastoid process. Arterioles in bone, the walls of the sigmoid sinus, and the posterior fossa dura coursed medially to supply the endolymphatic sac. The orientation of arterioles tended to be along the long axis of the endolymphatic duct and sac, whereas venules were more likely to be circumferentially oriented. Arterioles arising from dural vessels divided into deeper branches, which supplied periductal connective tissue, and superficial branches, which entered canaliculi of the vestibular aqueduct. Gross anatomic findings were confirmed by histologic examination of temporal bones.

The lateral skull base: a vascular perspective with clinical implications.

The growing number of options in the surgical management of skull base disease has renewed interest in the microvascular anatomy of the lateral temporal region. We studied this anatomy by injecting colored solutions of methyl methacrylate into the major blood vessels of six human cadaver heads or selectively into their major branches. We used several techniques to see the vascular anatomy and to study its relationship to the layers of the scalp. Results revealed that every anatomically named blood vessel was accompanied by a finer, deeper blood vessel supplying the periosteum and outer table of the skull. These vessels arborized into a network of capillaries in the periosteum adherent to the outer bony cortex, from which we saw tiny perforators entering bone. This layered blood supply has direct implications for both ablative and reconstructive surgery for skull base disease. We also saw a previously undescribed arterial plexus accompanying the commonly described venous plexus in the infratemporal fossa.

Cochlear nucleus anatomy related to central electroauditory prosthesis implantation.

The central electroauditory prosthesis is now used to stimulate the cochlear nuclei to obtain auditory perception in patients with bilateral cochlear nerve transection who are undergoing bilateral acoustic tumor removal. In this study, we used fixed cadaver specimens to identify visible landmarks for accurate placement of the central electroauditory prosthesis through a combined suboccipital-translabyrinthine opening. Histologic features of the regions of probable implantation of the central electroauditory prosthesis were also investigated. We found that the following landmarks might have surgical significance: (1) the tenia of the inferior velum of the fourth ventricle, which crosses the surface of the ventral cochlear nucleus and the vestibulocochlear nerve; (2) the angle between the vestibulocochlear and glossopharyngeal nerves; and (3) the foramen of Luschka. It is suggested that an incision be made in the tenia for insertion of the prosthesis into the lateral recess and eventual placement on the ventral cochlear nucleus surface. To study regions of potential stimulation, we injected ink into different sites on the exposed surface of the cochlear nuclei. We then histologically examined neuronal populations adjacent to the sites. We found that a portion of the ventral cochlear nucleus localized within the lateral recess might be the most appropriate location for placement of the central electroauditory prosthesis.

Axial temporomandibular joint morphology: a correlative study of radiographic and gross anatomic findings.

In degenerative diseases of the temporomandibular joint the mandibular condyle demonstrates changes in contour, including flattening and enlargement, resulting in an increased diameter of the articular surface. The purpose of this study was to determine if such alterations in the shape of the mandibular condyle can be visualized in submentovertex (axial) radiographs and correlated with pathologic changes of the temporomandibular joint. Submentovertex radiographs of 18 human cadaver specimens were made. The radiographic condylar dimensions, morphologic condylar outline, and angle of the condylar axis with respect to the transmeatal line were determined. The specimens were dissected and disarticulated, and radiographic findings were compared to anatomic structure. Osseous abnormalities were found in 21 of the 36 joints studied (58%). Perforations of the disk were found in nine of 31 joints (29%) investigated. No statistically significant differences between the normal condyles and condyles displaying osseous abnormalities were found in any of the radiographic parameters studied.