Contralateral Olfactory Bulb Research Articles

Air pollution nanoparticle and alpha-synuclein fibrils synergistically decrease glutamate receptor A1, depending upon nPM batch activity

BackgroundEpidemiological studies have variably linked air pollution to increased risk of Parkinson’s disease (PD). However, there is little experimental evidence for this association. Alpha-synuclein (α-syn) propagation plays central roles in PD and glutamate receptor A1 (GluA1) is involved in memory and olfaction function. MethodsEach mouse was exposed to one of three different batches of nano-particulate matter (nPM) (300 μg/m3, 5 h/d, 3 d/week), collected at different dates, 2017–2019, in the same urban site. After these experiments, these nPM batches were found to vary in activity. C57BL/6 female mice (3 mo) were injected with pre-formed murine α-synuclein fibrils (PFFs) (0.4 μg), which act as seeds for α-syn aggregation. Two exposure paradigms were used: in Paradigm 1, PFFs were injected into olfactory bulb (OB) prior to 4-week nPM (Batch 5b) exposure and in Paradigm 2, PFFs were injected at 4th week during 10-week nPM exposure (Batches 7 and 9). α-syn pSer129, microglia Iba1, inflammatory cytokines, and Gria1 expression were measured by immunohistochemistry or qPCR assays. ResultsAs expected, α-syn pSer129 was detected in ipsilateral OB, anterior olfactory nucleus, amygdala and piriform cortex. One of the three batches of nPM caused a trend for elevated α-syn pSer129 in Paradigm 1, but two other batches showed no effect in Paradigm 2. However, the combination of nPM and PFF significantly decreased Gria1 mRNA in both the ipsi- and contra-lateral OB and frontal cortex for the most active two nPM batches. Neither nPM nor PFFs alone induced responses of microglia Iba1 and expression of Gria1 in the OB and cortex. ConclusionExposures to ambient nPM had weak effect on α-syn propagation in the brain in current experimental paradigms; however, nPM and α-syn synergistically downregulated the expression of Gria1 in both OB and cortex.

Neuronal responses to focused ultrasound are gated by pre-stimulation brain rhythms

BackgroundOwing to its high spatial resolution and penetration depth, transcranial focused ultrasound stimulation (tFUS) is one of the most promising approaches to non-invasive neuromodulation. Identifying the impact of endogenous neural activity on neuromodulation outcome is critical to harnessing the potential of tFUS. ObjectiveHere we sought to identify the relationship between pre-stimulation neural activity and the neuronal response to tFUS. MethodsWe applied 3 min of continuous-wave tFUS to the hippocampal region of the rat while recording local field potentials (LFP) and multi-unit activity (MUA) from the target. We also tested the application of tFUS but with an air gap separating the transducer and the skull, as well as active stimulation of the contralateral olfactory bulb. ResultsWe observed a modest but significant increase in firing rate during hippocampal tFUS, but not during stimulation of the olfactory bulb or when an air gap was present. Importantly, the observed firing rate increase was significantly modulated by the power of baseline oscillations in the LFP, with low levels of delta (1–3 Hz) and high levels of theta (4–10 Hz) and gamma (30–250 Hz) power producing significantly larger firing rate increases. Firing rate increases were also amplified by a factor of 7× when stimulation was applied during periods of frequent sharp-wave ripple (SWR) activity. ConclusionOur findings suggest that baseline brain rhythms may effectively “gate” the response to tFUS.

Olfactory Bulb Microstructural Changes in Patients With Nasal Septum Deviation.

The aim of this study is to assess the microstructural changes to the olfactory bulb (OB) in patients with nasal septum deviation (NSD) using diffusion tensor imaging and to research the association between these changes and the degree of NSD. Ninety-six patients with NSD (46 males, 50 females) who received diffusion tensor imaging were assessed by 2 independent readers. The patients were separated into 3 groups according to the NSD angle. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of the ipsilateral and contralateral OB were measured in all NSD patients by region of interest. According to deviation side, there was significant difference between the right (R) and left (L) OB FA and ADC values across the 3 groups. In patients with left- and right- sided NSD, FA and ADC values for the left and right OB were significantly different between groups 1 and 3, and groups 2 and 3. There was negative correlation between L-FA (r = -0.481, P = 0.001; r = -0.496, P = 0.001) and R-FA (r = -0.705, P = 0.001; r = -0.286, P = 0.02) versus age and deviation angle. However, there was positive correlation between L-ADC versus age and deviation angle (r = 0.493, P = 0.001; r = 0.482, P = 0.001), as well as positive correlation between R-ADC versus age (r = 0.646, P = 0.001). This is the first study showing ADC increase and FA decrease associated with axonal damage and microstructural integrity loss based on the side of deviation in NSD patients. It has also shown that this abnormality is directly proportional with NSD degree.

Smell Preservation following Unilateral Endoscopic Transnasal Approach to Resection of Olfactory Groove Meningioma: A Multi-institutional Experience.

Introduction Olfactory groove meningiomas (OGMs) are often associated with loss of smell following resection. Loss of smell has a measurable impact on quality of life. Smell preservation has been previously described in open approaches for early stage or unilateral OGMs. Evidence of smell preservation in endoscopic approaches is lacking. Design A multi-institutional retrospective review was performed on consecutive patients who underwent unilateral endoscopic endonasal resection of OGM. A gross total resection was achieved with preservation of the contralateral olfactory cleft and bulb. Olfactory function was assessed with a six-point olfactory symptom score and the Sniffin' Sticks 12-item smell identification test (SS-12). Contralateral olfactory bulb volume was measured on postoperative magnetic resonance imaging. Results Four patients (age 42.0 ± 7.5, 75% female) were assessed. Olfactory function was assessed at 21.8 ± 5.6 months following surgery. All patients reported some degree of smell preservation (75% described a slight/mild impairment in smell or better). Olfactory identification was preserved with an SS-12 score of 9 ± 1.4 (anosmia defined as ≤6). The olfactory bulb volume was calculated to be 47.4 ± 15.9 mm 3 (normal >40 mm 3 ). Conclusion Smell preservation is possible following unilateral endoscopic endonasal resection of carefully selected OGM.

Myelination of the developing lateral olfactory tract and anterior commissure.

Both the lateral olfactory tract (LOT) and anterior limb of the anterior commissure (AC) carry olfactory information. The LOT forms the projection from the olfactory bulb to the ipsilateral olfactory cortices, while the AC carries odor information across the midline to the contralateral olfactory cortex and bulb. The LOT and AC differ on a number of dimensions, including early development and functional onset. The present work, examining their myelination in mice, reveals additional important differences. For example, the LOT initiates myelination 3-4 days earlier than the AC, evidenced by both an earlier increase in myelin basic protein staining seen with immunohistochemistry and an earlier appearance of myelinated fibers using electron microscopy. While both exhibit a period of rapid myelination, it occurs 4-5 days earlier in the LOT than the AC. The tracts also respond differently to early sensory restriction. Unilateral naris occlusion from the day after birth to postnatal day 30 had no consistent effects on the AC but resulted in significantly thinner myelin sheaths relative to axon caliber in the LOT. Finally, the two tracts differ structurally (the LOT contains larger, more densely packed axons with significantly thicker myelin sheaths resulting in a conduction velocity that is more than twice as fast as the AC). The findings indicate that these two large, accessible tracts provide an important means for studying brain maturation due to basic differences in both the timing of their maturation and general organization.

The Effect of Unilateral Concha Bullosa on Olfactory Bulb Volume: an Assessment by Magnetic Resonance Imaging.

In this study, the authors compared the right and left olfactory bulb volumes by magnetic resonance image findings of patients with unilateral concha bullosa (CB). The cranial magnetic resonance imaging studies of 24 patients having unilateral CB were reviewed. There were 10 males and 14 females ranging in age from 29 to 51 years (mean age, 29 ± 15.2 years). The volumes of both olfactory bulbs (contralateral and ipsilateral to the concha bullosa side) were calculated by using the computer program. The average values for olfactory bulb volumes were 46.57 ± 8.03 mm in the CB side of the nasal cavity and 54.80 ± 10.031 mm in the normal side of the nasal cavity. We found a statistically significant difference in olfactory bulb volume between the contralateral and ipsilateral to the concha bullosa side of the patients (t = -3.08 and P < 0.01 for CB side, t = -3.47 and P < 0.01 for left normal side). Our results may point out a possible relationship between CB and ipsilateral decreased olfactory bulb volume, yet the exact mechanism still remains unclear. Decreased nasal air flow on the CB side may be attributed to the pathophysiologic mechanism of this finding. Also, the significant reduction in olfactory bulb volumes ipsilateral to CB compared with the contralateral olfactory bulb volumes seems to support our hypothesis.

Treatment of pediatric esthesioneuroblastoma with smell preservation

Olfactory neuroblastoma is a rare malignant tumor of neuroectodermal origin and represents the most common cancer of the nasal cavity in pediatric age. The gold standard of treatment consists of en bloc resection, numerous studies have shown as the endoscopic approaches permit good control of the disease improving the quality of life after the treatment. Herein we describe the case of a 13-year-old patient referred to our outpatient clinic with a polypoid multi-lobed lesion occupying the left nasal cavity and imaging that confirmed a left-sided nasal mass without cribriform plate involvement (Kadish B). We performed an unilateral endoscopic resection with transnasal craniectomy and anterior skull base reconstruction with a flap from the contralateral nasal septum based on the septal branches of the anterior and posterior ethmoidal arteries (Septal Flip Flap, SFF), that provided a faster healing process with reduction of nasal crusting, improvement in the quality of life of patient in the postoperative period and the preservation of the contralateral olfactory bulb that has allowed to save the smell. This treatment strategy of pediatric esthesioneuroblastoma was analyzed in the context of the current literature.

Olfactory Bulb Volume Changes in Patients With Nasal Septal Deviation.

The olfactory bulb (OB) plays a pivotal role in the processing of olfactory information. The aim of this study was to investigate the OB volume changes and its possible associations with nasal septal deviation. Cross-sectional study. Otolaryngology Department of Bozok University School of Medicine and Neurology Department of Yozgat State Hospital. Ninety patient's cranial magnetic resonance imaging (MRI) studies (46 males and 44 females, mean age 36 ± 13.4 years; range 18-56 years) with isolated nasal septal deviations were recruited for the study. Olfactory bulb volumes in all study subjects were evaluated in T2-weighted coronal MRI images by planimetric manual contouring. Nasal septal deviation angles were found to range between 5° and 23.21° (mean 13.6° ± 3.58°). The right-sided deviations included 17 mild (<9°, Group I), 20 moderate (9°-15°, Group II), and 16 severe (15° and up, Group III) patients. The left-sided deviations included 14 mild (<9°, Group I), 13 moderate (9°-15°, Group II), and 10 severe (15° and up, Group III) subjects. Olfactory bulb volumes were calculated in both right- and left-sided deviation groups. In the patients with left-sided septal deviations of Groups I, II, and III, the left OB volumes of Groups I, II, and III were 46.49 ± 3.87, 47.46 ± 3.36, and 60.68 ± 5.65 mm and the right OB volumes were 53.37 ± 3.76, 56.47 ± 4.43, and 76.69 ± 6.84 mm, respectively. The statistical evaluation of the right OB volumes did not produce significant difference between Groups I and II (P = 0.73). The authors demonstrated statistically significant differences in comparison of Groups I to III and Groups II to III (P = 0.002 and P = 0.016, respectively). In the right septal deviation group for Groups I, II, and III, mean volumes of right OB volumes were 45.59 ± 4.46, 48.63 ± 3.78, and 61.35 ± 5.84 mm, respectively, and the left OB volumes were 54.67 ± 4.73, 57.65 ± 4.53, and 75.84 ± 7.67 mm, respectively. There was no statistically significant difference between Groups I and II (P = 0.95) left OB volumes in the right-sided deviation group, but statistically significant difference was demonstrated in Groups I to III and Groups II to III compartments (P = 0.002 and P = 0.003). In our study, while mild and moderate septal deviations lacked any significant affect on OB volumes, severe deviations were found to have significant impact on these parameter. Additionally the contralateral OB volumes in the severe septum deviation group were significantly bigger when compared to the ipsilateral OB volumes. Further multidisciplinary studies are required to evaluate the clinical significance of OB volume changes in diagnosis and follow-up of several otolaryngologic or nonotolaryngologic diseases.

Unilateral Expanded Endoscopic Endonasal Surgery for Olfactory Schwannoma of Anterior Cranial Base in a Patient with Hereditary Hemorrhagic Telangiectasia

Background and Importance: Olfactory schwannomas of the anterior skull base (ASB) are rare tumors and their association with hereditary hemorrhagic telangiectasia (HHT) has not previously been described. The majority of ASB schwannomas arise from the sinonasal tracts, and may demonstrate intracranial extension. We report a case with an olfactory schwannoma of the ASB with subpial involvement of the frontal lobe. Complete tumor resection was performed through a unilateral extended endonasal endoscopic approach with preservation of the contralateral olfactory bulb. Anterior cranial base repair was achieved with a unilateral contralateral mucoperichondrial vascularized pedicled nasoseptal flap.

Ipsilateral reduced olfactory bulb volume in patients with unilateral nasal obstruction.

To evaluate the effect of unilateral nasal obstruction (by nasal polyps of different histopathology) on olfactory bulb volume using MRI technique. Cross-sectional study. Tertiary university hospitals, Departments of Otolaryngology and Radiology. Eleven patients with a few months of complete unilateral nasal obstruction of different pathological etiologies were selected. MRI assessment of olfactory bulb volume was performed using planimetric manual contouring. The contralateral olfactory bulb was used as a comparative control for the same patient. Eleven healthy controls constituted the control group. Mean olfactory bulb volume ± SD of obstructed side = 14.3 ± 3.7 mm(3), mean olfactory bulb volume ± SD of nonobstructed side = 43.49 ± 10.7 mm(3). The difference between the 2 sides was significant (P = .003). The difference in olfactory bulb volume between normal subjects and nonobstructed nasal side was statistically nonsignificant (t = .9118, P = .3727), while the difference between normal subjects' olfactory bulb volume and obstructed nasal side olfactory bulb volume in our patients was extremely statistically significant (t = 9.7320, P < .0001). A strong negative correlation was found between duration of obstruction and olfactory bulb volume (R = -0.9761). This study shows that unilateral nasal obstruction may be associated with a lateralized ipsilateral difference of olfactory bulb volume.

Diversity among principal and GABAergic neurons of the anterior olfactory nucleus.

Understanding the cellular components of neural circuits is an essential step in discerning regional function. The anterior olfactory nucleus (AON) is reciprocally connected to both the ipsi- and contralateral olfactory bulb (OB) and piriform cortex (PC), and, as a result, can broadly influence the central processing of odor information. While both the AON and PC are simple cortical structures, the regions differ in many ways including their general organization, internal wiring and synaptic connections with other brain areas. The present work used targeted whole-cell patch clamping to investigate the morphological and electrophysiological properties of the AON's two main neuronal populations: excitatory projection neurons and inhibitory interneurons. Retrograde fluorescent tracers placed into either the OB or PC identified projection neurons. Two classes were observed with different physiological signatures and locations (superficial and deep pyramidal neurons), suggesting the AON contains independent efferent channels. Transgenic mice in which GABA-containing cells expressed green fluorescent protein were used to assess inhibitory neurons. These cells were further identified as containing one or more of seven molecular markers including three calcium-binding proteins (calbindin, calretinin, parvalbumin) or four neuropeptides (somatostatin, vasoactive intestinal peptide, neuropeptide Y, cholecystokinin). The proportion of GABAergic cells containing these markers varied across subregions reinforcing notions that the AON has local functional subunits. At least five classes of inhibitory cells were observed: fast-spiking multipolar, regular-spiking multipolar, superficial neurogliaform, deep neurogliaform, and horizontal neurons. While some of these cell types are similar to those reported in the PC and other cortical regions, the AON also has unique populations. These studies provide the first examination of the cellular components of this simple cortical system.

Efferent and afferent connections of the olfactory bulb and prepiriform cortex in the pigeon (Columba livia)

Although olfaction in birds is known to be involved in a variety of behaviors, there is comparatively little detailed information on the olfactory brain. In the pigeon brain, the olfactory bulb (OB) is known to project to the prepiriform cortex (CPP), piriform cortex (CPi), and dorsolateral corticoid area (CDL), which together are called the olfactory pallium, but centrifugal pathways to the OB have not been fully explored. Fiber connections of CPi and CDL have been reported, but those of other olfactory pallial nuclei remain unknown. The present study examines the fiber connections of OB and CPP in pigeons to provide a more detailed picture of their connections using tract-tracing methods. When anterograde and retrograde tracers were injected in OB, projections to a more extensive olfactory pallium were revealed, including the anterior olfactory nucleus, CPP, densocellular part of the hyperpallium, tenia tecta, hippocampal continuation, CPi, and CDL. OB projected commissural fibers to the contralateral OB but did not receive afferents from the contralateral olfactory pallium. When tracers were injected in CPP, reciprocal ipsilateral connections with OB and nuclei of the olfactory pallium were observed, and CPP projected to the caudolateral nidopallium and the limbic system, including the hippocampal formation, septum, lateral hypothalamic nucleus, and lateral mammillary nucleus. These results show that the connections of OB have a wider distribution throughout the olfactory pallium than previously thought and that CPP provides a centrifugal projection to the OB and acts as a relay station to the limbic system.

Olfacto-retinalis pathway in Austrolebias charrua fishes: A neuronal tracer study

The olfacto-retinal centrifugal system, a constant component of the central nervous system that appears to exist in all vertebrate groups, is part of the terminal nerve (TN) complex. TN allows the integration of different sensory modalities, and its anatomic variability may have functional and evolutionary significance. We propose that the olfacto-retinal branch of TN is an important anatomical link that allows the functional interaction between olfactory and visual systems in Austrolebias. By injecting three different neuronal tracers (biocytin, horseradish peroxidase, and 1,1′-dioctadecyl-3,3,3′,3′tetramethyl-indocarbocyanine perchlorate (DiI)) in the left eye of Austrolebias charrua fishes, we identified the olfacto-retinal branch of TN and related neuronal somas that were differentiable by location, shape, and size. The olfacto-retinal TN branch is composed of numerous thin axons that run ventrally along the olfactory bulb (OB) and telencephalic lobes, and appears to originate from a group of many small monopolar neurons located in the rostral portion of both the ipsi- and contralateral OB (referred to as region 1). Labeled cells were found in two other regions: bipolar and multipolar neurons in the transition between the OB and telencephalic lobes (region 2) and two other groups in the preoptic/pretectal area (region 3). In this last region, the most rostral group is constituted by monopolar pear-shaped neurons and may belong to the septo-preoptic TN complex. The second group, putatively located in the pretectal region, is formed by pseudounipolar neurons and coincides with a conserved vertebrate nucleus of the centrifugal retinal system not involved in the TN complex. The found that connections between the olfactory and visual systems via the olfacto-retinal TN branch suggest an early interaction between these sensory modalities, and contribute to the identification of their currently unknown circuital organization.

“How Much Is Enough?” Endonasal Surgery for Olfactory Neuroblastoma

“How Much Is Enough?” Endonasal Surgery for Olfactory Neuroblastoma

Acute sodium tungstate inhalation is associated with minimal olfactory transport of tungsten ( 188W) to the rat brain

Olfactory transport of represents an important mechanism for direct delivery of certain metals to the central nervous system (CNS). The objective of this study was to determine whether inhaled tungsten (W) undergoes olfactory uptake and transport to the rat brain. Male, 16-week-old, Sprague–Dawley rats underwent a single, 90-min, nose-only exposure to a Na 2 188WO 4 aerosol (256 mg W/m 3). Rats had the right nostril plugged to prevent nasal deposition of 188W on the occluded side. The left and right sides of the nose and brain, including the olfactory pathway and striatum, were sampled at 0, 1, 3, 7, and 21 days post-exposure. Gamma spectrometry ( n = 7 rats/time point) was used to compare the levels of 188W found on the left and right sides of the nose and brain and blood to determine the contribution of olfactory uptake to brain 188W levels. Respiratory and olfactory epithelial samples from the side with the occluded nostril had significantly lower end-of-exposure 188W levels confirming the occlusion procedure. Olfactory bulb, olfactory tract/tubercle, striatum, cerebellum, rest of brain 188W levels paralleled blood 188W concentrations at approximately 2–3% of measured blood levels. Brain 188W concentrations were highest immediately following exposure, and returned to near background concentrations within 3 days. A statistically significant difference in olfactory bulb 188W concentration was seen at 3 days post-exposure. At this time, 188W concentrations in the olfactory bulb from the side ipsilateral to the unoccluded nostril were approximately 4-fold higher than those seen in the contralateral olfactory bulb. Our data suggest that the concentration of 188W in the olfactory bulb remained low throughout the experiment, i.e., approximately 1–3% of the amount of tungsten seen in the olfactory epithelium suggesting that olfactory transport plays a minimal role in delivering tungsten to the rat brain.

Contralateral projections of the rat anterior olfactory nucleus.

The anterior olfactory nucleus (AON) is a central olfactory cortical structure that has heavy reciprocal connections with both the olfactory bulb (OB) and piriform cortex. While it has been firmly established that the AON is a primary source of bilateral projections in the olfactory system through extensive connections with both the ipsilateral and contralateral OB, AON, and piriform cortex, few studies have examined this circuitry in detail. In the present study we used small injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde tracer FluoroGold in specific subregions of the AON to explore the topography of the interconnections between the left and right AONs. Labeled fibers were found in the contralateral AON following injections in all areas. However, detailed quantitative analyses revealed that different regions of the AON have distinct patterns of interhemispheric innervation; contralateral fibers were most heavily targeted to dorsal and lateral AON subregions, while the medial and ventral areas received relatively light projections. These results demonstrate important features of the interhemispheric circuitry of the AON and suggest separate functional roles for subregions of the AON in olfactory information processing.

A Circadian Clock in the Olfactory Bulb Controls Olfactory Responsivity

Recently, it has been shown that multiple mammalian cell types express daily rhythms in vitro. Although the suprachiasmatic nucleus (SCN) of the hypothalamus is known to regulate a wide range of circadian behaviors, the role for intrinsic rhythmicity in other tissues is unknown. We tested whether the main olfactory bulb (OB) of mice mediates daily changes in olfaction. We found circadian rhythms in cedar oil-induced c-Fos, a protein marker of cellular excitation, in the mitral and granular layers of the OB and in the piriform cortex (PC). These oscillations persisted in constant darkness with a fourfold change in amplitude and a peak approximately 4 h after the onset of daily locomotor activity. Electrolytic lesions of the SCN abolished circadian locomotor rhythms, but not odor-induced c-Fos rhythms in the OB or PC. Furthermore, removal of the OB abolished spontaneous circadian cycling of c-Fos in the PC, shortened the free-running period of locomotor rhythms, and accelerated re-entrainment after a 6 h advance and slowed re-entrainment after a 6 h delay in the light schedule. OB ablation or odorant altered the amplitude of c-Fos rhythms in the SCN and ablation of one OB abolished c-Fos rhythms in the ipsilateral PC, but not in the contralateral OB and PC. We conclude that the OB comprises a master circadian pacemaker, which enhances olfactory responsivity each night, drives rhythms in the PC, and interacts with the SCN to coordinate other daily behaviors.

Changes in the serotonergic system in the main olfactory bulb of rats unilaterally deprived from birth to adulthood

The serotonergic system plays a key role in the modulation of olfactory processing. The present study examined the plastic response of this centrifugal system after unilateral naris occlusion, analysing both serotonergic afferents and receptors in the main olfactory bulb. After 60 days of sensory deprivation, the serotonergic system exhibited adaptive changes. Olfactory deprivation caused a general increase in the number of fibres immunopositive for serotonin but not of those immunopositive for the serotonin transporter. HPLC data revealed an increase in serotonin levels but not in those of its major metabolite, 5-hydroxyindole acetic acid, resulting in a decrease in the 5-hydroxyindole acetic acid/serotonin ratio. These changes were observed not only in the deprived but also in the contralateral olfactory bulb. Double serotonin-tyrosine hydroxylase immunolabelling revealed that the glomerular regions of the deprived olfactory bulb with a high serotonergic fibre density showed a strong reduction in tyrosine hydroxylase. Finally, the serotonin(2A) receptor distribution density and the number of juxtaglomerular cells immunopositive for serotonin(2A) receptor remained unaltered after olfactory deprivation. Environmental stimulation modulated the serotonergic afferents to the olfactory bulb. Our results indicate the presence of a bilateral accumulation of serotonin in the serotonergic axon network, with no changes in serotonin(2A) receptor density after unilateral olfactory deprivation.

Transfer of Some Carboxylic Acids in the Olfactory System Following Intranasal Administration

The uptake of [14C]benzoic acid, 4-chloro[14C]benzoic acid, [3H]phthalic acid and [14C]salicylic acid in the nasal passages and brain was determined following a unilateral intranasal instillation in mice. An uptake of radioactivity from the nasal mucosa to the ipsilateral olfactory bulb was observed up to 4 h after administration following intranasal instillation of these carboxylic acids whereas the level was low in the contralateral olfactory bulb. Autoradiography of mice given [14C]benzoic acid and [14C]salicylic acid by intranasal instillation showed a preferential localization of radioactivity in the axonal and glomerular layer of the olfactory bulb 1 h after the administration. Four hours after administration the radioactivity was present as a gradient from the axonal layer towards the center of the olfactory bulb. Pretreatment of mice with a compound known to damage the olfactory neuroepithelium resulted in a decreased uptake of [14C]benzoic acid in the olfactory bulb. Thin layer chromatography of supernatants from the ipsilateral olfactory bulbs of mice given [14C]benzoic acid by nasal instillation indicated that the radioactivity in the bulbs represented unchanged compound. These results suggest that there is a transfer of some aromatic carboxylic acids in the olfactory pathways.

Lidocaine distribution into the CNS following nasal and arterial delivery: a comparison of local sampling and microdialysis techniques

The disposition of lidocaine within the CNS of the rat following nasal and intra-arterial delivery was characterized using a microdialysis technique. Lidocaine concentrations in the cisterna magna were determined using microdialysis and compared to those previously determined using a direct CSF sampling method. The disposition profiles for lidocaine into the cisternal CSF obtained using microdialysis were found to be similar to those obtained by direct CSF sampling techniques over an initial 120-min interval. In other experiments, lidocaine disposition in the right (dosed side) and left olfactory bulb following nasal (i.n.) and intra-arterial (i.a.) administration was studied using microdialysis. The lidocaine concentrations in the ipsilateral olfactory bulb were slightly higher after drug administration into the nasal cavity than those in the contralateral olfactory bulb over the initial 20-min sampling interval. Drug concentrations found in the right olfactory bulb were not significantly different from those found in the left olfactory bulb following intra-arterial administration. Comparisons of lidocaine disposition in the right olfactory bulb and cerebellum, two CNS sites with the same regional vascular supply, showed that the disposition patterns were nearly identical for the two sites following i.a. administration. There was a significant lengthening in the t max at both sites following i.n. delivery compared to i.a. delivery, and the relative concentrations at each site were no longer equivalent. From these results, it appears that the microdialysis technique is a useful tool for studying drug distribution into the CNS. The changes in disposition patterns between i.a. and i.n. administration indicate that other factors or pathways, in addition to the systemic circulation, play a role in the transport of lidocaine into the brain following nasal administration.