J Drug Target 1998;5(6):415-41
Nasal route for direct delivery of solutes to the central nervous system:
fact or fiction?
Mathison S, Nagilla R, Kompella UB
Department of Chemistry, Auburn University, AL 36849-5503, USA.
[Medline record in process]
During this century, several investigators reported that certain viruses,
metals, drugs, and other solutes could bypass systemic circulation and enter
the brain and/or cerebrospinal fluid directly following nasal
administration. Although evidence clearly suggests that the olfactory
epithelium and its olfactory cells play a major role, little is known about
the mechanisms of direct transport of solutes into the brain. An overview of
what is known about these mechanisms may aid in further research in this
field, including studies of direct drug delivery to the central nervous
system. This review, in addition to summarizing the literature to date,
clearly describes the intricate association of the anatomical features
involved in direct entry of solutes into the brain following nasal
administration. To aid in the understanding of the possible routes a solute
can take after nasal administration, the anatomy of the olfactory epithelium
and surrounding tissues is described, and a detailed scheme delineating the
emerging pathways is presented. Techniques used in delineating these
pathways and studies supporting a particular pathway are discussed in
greater detail. Finally, some factors influencing the direct transport of
solutes to the cerebrospinal fluid and brain are summarized.
PMID: 9783675, UI: 98454996
Ann Fr Anesth Reanim 1998;17(2):144-8
[The cerebral venous outflow tract].
[Article in French]
Grevy V, Escuret E
Departement d'anesthesie-reanimation B, hopital Saint-Eloi, Montpellier,
It is generally assumed that the jugular veins are the only significant path
for cerebral venous drainage. Little attention has been given to the
possible role of other venous paths for the cerebral venous outflow. In
fact, the meningorachidian venous plexus acts as the major outflow tract of
cerebral circulation in the upright position. This phenomenon is linked with
postural variations in cerebrospinal fluid pressure. It is difficult to
assess the significance of this posterior venous plexus under
physiopathologic conditions, which probably depends on the extent of the
anastomoses between the two systems.
? Review, tutorial
PMID: 9750712, UI: 98423286
Anesth Prog 1993;39(6):209-11
Effect of head-down tilt on intracranial pressure and sagittal sinus
pressure during general anesthesia in cats.
Kotani J, Momota Y, Sugioka S, Umemura A, Ueda Y
Department of Anesthesiology, Osaka Dental University, Japan.
The effect of head-down tilt during general anesthesia on intracranial
pressure (ICP) dynamics was examined in eight cats. Changes in lateral
ventricular pressure (LVP), sagittal sinus pressure (SSP), and effective CSF
pressure (ECSFP), which is the driving pressure of cerebrospinal fluid (CSF)
absorption, were studied in association with a shift from the horizontal
prone position to the 20 degrees head-down tilt position. Both LVP and SSP
values were significantly (P < 0.01) increased at 10 min in the head-down
tilt position as compared with the control position, remained elevated
during the next 110 min, and returned to baseline when the horizontal
position was restored. However, ECSFP (expressed by LVP - SSP) was not
significantly different from the control value, because changes in LVP and
SSP were similar. These results suggest that head-down tilt does not impair
PMID: 8250342, UI: 94071203
Comp Biochem Physiol A 1986;83(2):207-11
Does gravitational pressure of blood hinder flow to the brain of the
Vascular pressure consists of the sum of two pressures: (a) pressure
developed by the pumping of the ventricles against the resistance of
vessels, designated as viscous flow pressure, and (b) pressure caused by
gravity, traditionally called hydrostatic, better described as gravitational
pressure. In a conduit, both of these pressures must be overcome when a
liquid is discharged to a higher level of gravitational potential energy. If
a liquid is returned to its original level, gravity neither helps nor
hinders flow because of the siphon effect. This circumstance prevails in the
circulatory system. Hence, P1-P2 in the Poiseuille equation excludes
gravitational pressure between those points. The long neck of the giraffe,
therefore, poses no impediment to blood flow in the erect posture. The
giraffe has a high aortic pressure. This is not for driving the blood to its
head but is for minimizing the gravitational drop of intravascular pressure
and collapse of the vessels. The cerebral circulation is protected by the
cerebrospinal fluid which undergoes parallel changes in pressure with
posture. Other vessels in the head are less protected by connective tissue,
surrounding muscles and other structures. The high aortic pressure in the
giraffe is probably caused by the high total peripheral resistance of the
systemic circuit due to vascular adaptations related to the overall height
of the animal.
PMID: 2869860, UI: 86163084
Tierarztl Prax 1989;17(1):97-100
[The immobilization of giraffes].
[Article in German]
Wiesner H, von Hegel G
Munchner Tierpark Hellabrunn.
The anatomical and physiological conditions of blood circulation in the
giraffe are pointed out. 16 immobilizations in the giraffe of either sex are
reported, of which 10 were immobilized according to the following scheme. 1.
Premedication: 30 mg Xylazine 150 mg Hyaluronidase 2. 15 minutes later a
halter with two long ropes is put on to hold up the animals' heads after
they lay down. 3. 20 minutes after premedication the injection of 5.6-6.0 mg
Etorphine (2.5-2.7 ml Immobilon) together with 150 I.U. Hyaluronidase
follows. 4. We think that the most important fact is to hold the animals
head and neck in an upright position during the whole time of
immobilization. 5. Within 3 to 5 minutes after the intravenous application
of 15 mg Diprenorphine (5.0 ml Revivon) the animals raise without any
PMID: 2718168, UI: 89242651
Am J Physiol 1989 Feb;256(2 Pt 2):R567-71
Siphon mechanism in collapsible tubes: application to circulation of the
Hicks JW, Badeer HS
Department of Physiology, School of Medicine, Creighton University, Omaha,
Controversy exists over the principles involved in determining blood flow to
the head of a giraffe, specifically over the role of gravity pressure (pgh)
in the collapsible jugular vein in facilitating uphill flow in arteries.
This study investigated the pressures within vertically oriented models
containing both rigid and collapsible tubes. An inverted U tube was
constructed (height = 103 cm) of thick rubber tubing in the ascending limb
and collapsible dialysis tubing in the descending limb. Water flow was
induced by a variable speed pump maintained at the reservoir level such that
the descending limb was partially collapsed. Pressure measurements were made
at various levels within the U tube by two methods: 1) with the transducer
at same level as the tip of the water-filled catheter and 2) with the
transducer at the reservoir level. During flow, the pressure at any point
was nearly atmospheric along the length of the descending limb. Such methods
of obtaining pressure indicated that the pressure gradient within the
partially collapsed descending limb was the sum of viscous flow pressure
(P1-P2 of Poiseuille) and gravitational pressure (pgh). To study the
facilitatory effect of a siphon, the descending limb was compared with a
horizontally placed limb (length = 100 cm), and the flow was kept constant.
Calculations of hydraulic "work" (pressure x flow) indicated that with a
partially collapsed descending limb, work of the pump was reduced by 15%
compared with uphill flow to the elevated horizontal position. It is
concluded that the siphon mechanism operates in a partially collapsed
descending limb of a siphon loop.
PMID: 2916707, UI: 89132871
Blood Vessels 1988;25(6):299-307
Sympathetic innervation of the cardiovascular system in the giraffe.
Nilsson O, Booj S, Dahlstrom A, Hargens AR, Millard RW, Pettersson KS
Institute of Neurobiology, University of Goteborg, Sweden.
The extreme blood pressure gradients in the giraffe, produced by gravity and
behaviour, present a special challenge to blood flow and vascular capacity
regulation, e.g. via sympathetic nerves. We report the distribution of
nerves in vascular tissue from giraffe extremities and neck based on
immunofluorescence against specific antisera to dopamine-beta-hydroxylase,
neuropeptide Y, neurofilament, and synapsin I. Sympathetic innervation of
gravitation-dependent arteries in the limbs was restricted to the
adventitia-media border, while in carotid arteries fibers penetrated deep
into the media. Surprisingly, limb veins appeared to be devoid of
sympathetic innervation, while jugular veins had a sparse innervation. The
morphological response, medial hypertrophy, that parallels the hydrostatic
pressure gradients in the circulation combines with the thick skin and tight
underlying fascia, the 'g-suit', and an exquisitely distributed sympathetic
innervation pattern to provide an effective array of mechanisms for
cardiovascular regulation in the adult giraffe.
PMID: 3203141, UI: 89076982
Anat Rec 1991 Jul;230(3):369-77
The structural organization and adrenergic innervation of the carotid
arterial system of the giraffe (Giraffa camelopardalis).
Kimani JK, Opole IO
Department of Human Anatomy, University of Nairobi, Kenya.
The sympathetic innervation of the giraffe (Giraffa camelopardalis) carotid
arterial system is described in this study using the sucrose-potassium
phosphate-glyoxylic acid (SPG) method. The brachiocephalic and bicarotid
trunks showed a paucity of sympathetic innervation. Smooth muscle nests
observed in the outer layers of the tunica media in these arteries revealed
a rich network of sympathetic nerve fibres. The common carotid artery showed
numerous sympathetic nerve fibres particularly in the outer muscular zone of
the tunica media. The internal maxillary, ramus anastomoticus, and arteria
anastomotica also revealed a rich sympathetic innervation and a deep
penetration of the nerve fibres into the tunica media. It is suggested that
the rich sympathetic innervation of the giraffe carotid arteries maintains a
basal tonic state in the smooth muscle in the tunica media. This, in turn,
may enable the animal to maintain a relatively high rate of blood flow in
the carotid arteries in diastole despite the pressure run-off. It is further
suggested that the muscular structure and dense sympathetic innervation of
the internal maxillary and its branches to the carotid rete mirabile provide
the animal with an array of mechanisms to modulate its cranial circulation
particularly when it bends its head to drink.
PMID: 1867411, UI: 91328438
Andrew K Fletcher <gravitystudy at hotmail.com> wrote in message
news:37a228f2.0 at news1...
> Has anyone on this group spotted the connection with gravity and
> cerebrospinal fluid circulation?
>> I could not believe my eyes when I read this on the als newsgroup.
>> The fact that altering the molecular weight of a substance has been shown
> enable it to enter the cerebrospinal fluid, not only supports my theory of
> gravity driven circulation, but provides irrefutable and totally
> evidence from competant professional medical researchers
> One of the main hurdles will be in delivery of the drug. The brain and
> system have their own circulation of cerebro-spinal fluid, which is almost
> completely separate from the blood system. Because of this, it has always
> difficult to get drugs in to the brain.
>> Treatments injected into a vein won't travel to the brain, and it is
> and difficult to inject drugs into the spinal fluid.
>>> Working with Dr Surindar Cheema from the Anatomy Department at Monash
> University, Dr Barrett has developed a delivery system that can get the
> the brain, or the site of injury in the spine. "We are optimistic that we
> modify the drug so that it will get across the blood-brain barrier - and
> have evidence of this already," he says. The modification, which
> targets p75 - has been patented. "The results have been stunning. In
> experimental rats with (experimentally induced) Motor Neurone Disease, we
> achieved 90 per cent recovery," he says. Motor Neurone Disease is a
> particularly debilitating illness, killing one Australian every day.
>>> In attempting to develop treatments for diseases of the central nervous
> the "blood-brain barrier" has presented a major difficulty. This is the
> natural defence system which has the function of preventing potentially
> substances from penetrating into the brain and spinal cord.
>> Dr Barrett and his colleagues Dr Surindar Cheema and Kim Lowry of the
> Department at Monash University have developed a revolutionary new
> which specifically targets the p75 molecule and prevents the "suicide" of
> Further, by altering the molecular weight of this anti p75 substance, they
> overcome the blood-brain barrier, thus allowing the drug to penetrate to
> brain and spinal cord.
>> Subj: Re: FW: PalsCals
> Date: 11/3/98 3:47:42 PM Pacific Standard Time
> From: D.Burke at unsw.edu.au (David Burke)
> To: walker at zeta.org.au (Grahame Walker)
> CC: ozpals at onelist.com ('___Ozpals'), colmills at magna.com.au ('_Colin
> Mills'), dscrt at one.net.au ('__Jenny Chung'), EHeppler at aol.com ('_Edie
> Heppler'), jim_compton at OU.EDU ('_Jim Compton'), mndvic at vicnet.net.au> ('___Rod
> Harris MNDA(Vic)'), pdbower at northnet.com.au ('___Phil Bower MNDA(NSW)'),
>rbalsdon at walldata.com ('_Robin Balsdon')
>> EHeppler <eheppler at aol.com> wrote in message
> news:19990727000019.23996.00000037 at ng-fm1.aol.com...> > Subj: Positive WIN News
> > Date: 1/10/99 11:35:23 AM Pacific Standard Time
> > From: Zcunning
> > To: EHeppler
> Message Board Title: "INCLINED TO SLEEP INCLINED"