Pax1/Foxa2- 1 of the primary genetic reasons why we balding men- are balding

[eldarlmario]

ok- taking an angle from this study(scoliosis) and combining the information from Dr Cotsarelis own research on PGD2(from where the concept of using a CRTh2 inhibitor for AGA came from- and proven indeed accurate by others and myself through feeling the difference it made to our scalps) and Cd34/IntergrinA6/CD200(the study that lists out the differences between balding- scalp and haired scalped from the same indidivuals(s)) plus some individual studies like the korean and japanese 1s that showed how Dkk1 inhibits hair growth, how tgf beta 2 induces catagen, how bmp-2 and ephrin a3 is downregulated in balding hair follicles, etc;

I find that the findings(on genes involved, upregulated/downregulated, etc) from them:

1)The Scoliosis study
2)Dr Cotasarelis PGD2 and Cd34/IntergrinA6/CD200 studies
3)Some individual studies by others

correlates with each other rather accurately.

In other words, like i have mentioned before:

Whatever all these truckload of binding site-altered genes(caused by the disruption of a so-called "PEC7 Enhancer" at the PAX1/FOXA2 locus) are doing:

TATA
HNF4
RAR
RXRA
STAT
BATF
COMP
VDR
HDAC2
CART1
FOXA
FOXP1
GATA3
H6 family homeobox 2
IRF
PAX5
P300

is leading to this downregulation of CD34, IntergrinA6(i ommited this in the post a few pages back) and CD200 on the balding scalp + Cd200 on the balding skull(and eyebrows for me)

Coupled with the fact that i myself indeed have a natural v-shape hairline before i started receding, slightly-curved spine and frequently-occuring parotitis of my parotid glands(just below the ears) and frequently-ocurring tinittus in my ears(mentioned very early in this thread months ago before i even stumbled on the scoliosis study) plus slight tingling sensation on my scalp temple when i massaged the lymph nodes below my jawline, ears and parathyroid glands on my neck made me feel the findings from the scoliosis study are extremely accurate.

P.S I also have occasional 'twiches" in my head that felt like some nerves were being 'twisted' whenever i adjusted my jaw or moved my neck- and again, this started during puberty but i am unsure of what the cause is and if there is any link to the balding haplotype variants.

-------------------------

[eldarlmario]

PPAR receptors and their relationship with RXRA:

Pax1(-)RXRA (DOWN) => RXRA/PPAR alpha + PPAR beta/RXRA + RXRA/PPAR gamma coactivation (DOWN) => Vitamin D Receptor:



The diagram shows how individual PPARs binds with RXRA

PPAR Beta is the 'master regulator' of sebocyte profileration and differentiation. IMO, there is nothing wrong with PPAR Beta expression. But due to certain modified functions in PPAR Alpha and/or PPAR gamma via interactions with RXRA- final gene transcription thru the VDR receptor favors sebocyte differentiation at the expense of adipocyte differentiation = more sebum and less fats on the balding scalp




Whatever the mechanism is, there is for certain(atually, it's already been indicated as being the genes with their binding sites altered by the Scoliosis study- so it's not just my own opinion), a modified function of the genes implicated in this section of the pathway that is a major cause of AGA- because they influence how downstream pathways behave- including but not limited to WNT/signalling pathway like DKK1, BMP-signalling like BMP-2, TGF Beta signalling like TGF Beta 1, TH1/Th2 cytokines ratio and activity, intracellular calcium levels, etc, etc
Calcitirol => VDR =>Vitamin D binding protein(this step can be bypassed by using topical Calcitirol directly to the scalp http://en.wikipedia.org/wiki/Vitamin_D-binding_protein ) => RXRA + RXRB(not stated as being altered in the balding haplo type) => VDR Activation => VDR target genes (VDR activation/inactivation has significant consequences on the immune system) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597838/

VDR TARGET GENES Classical VDR Targets The most striking effect of severe vitamin D defi-ciency is rickets. Rickets can also result from mutations in theCYP27B1 or theVDR gene. 1,25(OH)2D3 is essen-tial for adequate Ca2þand Pi absorption from the intes-tine and hence for bone formation [112]. Liganded VDR has been shown to induce expression of the gene encod-ing for the major Ca2þ channel in intestinal epithelial cell, transient receptor potential cation channel, subfamily V, member 6 (TRPV6), by direct binding to a VDRE at 1.2, 2.1 and 4.3 kb from the TSS [113]. The sodium-phos-phate transport protein 2B (SLC34A2) gene was also found to be induced by 1,25(OH)2D3although no VDREs have yet been identified for this gene [114]. 1,25(OH)2D3 also down-regulates the expression of the PTH gene that opposes 1,25(OH)2D3 in regulation of serum Ca2þ and Pi levels, but up-regulates the fibroblast growth factor 23 (FGF23) gene(as posted before, this unheard of FGF has atually got alot to do with the hair), whose gene product, like PTH, lowers serum Pi levels [115]. The induction of the tumor necrosis factor ligand superfamily, member 11 (TNFSF11, also called RANKL) gene by liganded VDR via multiple distant VDREs (up to 76 kb from the TSS) leads to stimulation of osteoclast precursors to fuse and form new osteoclasts, resulting in enhanced resorption of bone [116]. Thus, this study also confirms that functional VDREs can be a large distance from the target gene TSS.

[eldarlmario]

ok i know people hate staring at a huge wall of text- so here goes:

VDR Targets in Cell Cycle Regulation

The main antiproliferative effect of 1,25(OH)2D3 on cells is a cell cycle block at the G1 phase. This can be explained by changed expression of multiple cell cycle regulator genes. Among the first targets described, expression of cyclin-dependent kinase inhibitor (CDKI) genes CDKN1A (also called p21) and CDKN1B (also called p27)(upregulates cell cycle arrest genes) were found to be up-regulated by ligand treatment [117,118]. For theCDKN1A gene, a VDRE in the proximal promoter was characterized, thus estab-lishing CDKN1A as a direct 1,25(OH)2D3 target gene [119]. More recently, it has been questioned whether CDKN1A actually represents a primary or a secondary target, the latter process via up-regulation of TGF-b or IGFBP3, and whether the described VDRE is truly func-tional [120,121]. Indeed, by screening 7 kb of the CDKN1A promoter with overlapping ChIP regions, three novel regions with 1,25(OH)2D3-induced VDR enrichment were identified, two of which also bound p53 as well [80]. The functionality of these characterized 1,25(OH)2D3-responsive regions relative to CDKN1A expression was illustrated through ChIP and 3C anal-yses [25,29]. Additional CDKIs, such asCDKN2B (p15), CDKN2A (p16), CDKN2C (p18), and CDKN2D (p19), also show transcriptional response to 1,25(OH)2D3, although the CDKN2A response appears to be secondary as it can be blocked by protein synthesis inhibitors [119,122]. In addition, the genes cyclin E1 (CCNE1), cyclin D1 (CCND1), and cyclin-dependent kinase 2 (CDK2) were also found to be down-regulated by 1,25 (OH)2D3 [120].(downregulated cell cycle progression genes) It remains to be elucidated whether these effects are primary and occur via functional VDREs on regulatory regions of these genes. Another interesting 1,25(OH)2D3 target gene isCCNC. The cyclin C-CDK8 complex was found to be associated with the RNA polymerase II basal transcriptional machinery [123] and is considered to be a functional part of mediator protein complexes that are involved in gene repression [124]. The fact that the CCNC gene, being located inchromosome6q21, is deleted in a subset of acute lymphoblasticleukemias,suggeststhatitmaybeinvolved in tumorigenesis [125]. In addition,growth arrest and DNA-damage-inducible, alpha (GADD45A) and members of the IGFBP gene family also respond to 1,25(OH)2D3 [81,126]. GADD45A plays an essential role in DNA repair and GADD45 proteins displace cyclin B1 from Cdc2 and hus inhibit the formation of M phase-promoting factor that is essential for G2/M transition [127].GADD45Ahas been shown to be a direct transcriptional target of 1,25 (OH)2D3 with a functional VDRE within the fourth exon of the gene [128]. IGFBPs modulate the activity of the circulating insulin-like growth factors (IGF) I and II. The IGFBP3 gene was first discovered to be up-regulated by 1,25(OH)2D3 and contains a functional VDRE [129]. As described above, IGFBP1 and IGFBP5 are also primary 1,25(OH)2D3 target genes [81]. Another interesting primary 1,25(OH)2D3 target is the PPARD gene(PPAR Beta, 'master regulator' of sebocyte profileration and differentiation), which contains a potent DR3-type VDRE in close proximity to its TSS [130]. PPARd and VDR proteins are widely expressed and in an apparent overlap in the physiological action of the two nuclear receptors, both are involved in the regulation of cellular growth, particularly neoplasms. HighPPARDexpression in tumor seems to be positive for the prognosis of associated cancers [131]. Overall, 1,25(OH)2D3 restricts cell cycle progression in several phases via multiple and partially redundant targets on parallel pathways that when combined provide a robust antiproliferative effect.

Relative Expression of VDR Target Genes The steady state mRNA expression levels of some VDR target genes, such as that of the CYP24A1 gene, are very low in the absence of ligand, but are induced up to 1000-fold by stimulation with 1,25(OH)2D3 [36]. Most other known primary 1,25(OH)2D3 target genes, such asCCNCandCDKN1A, often show an inducibility of twofold or less after short-term treatment with 1,25 (OH)2D3 [132,133]. These latter genes, however, exhibit 10 000e100 000-fold higher(the enzyme that converts Calcitirol to its inactive metabolite- thus rendering circulating Calcitirol biologically incapable of doing anything- even though there has been a study that stated that the inactive metabolite has a still unknown receptor of its own in the bones) basal expression levels as compared to that of theCYP24A1 gene. Thus, when the relative levels are taken into account, two- to 20-fold moreCCNCandCDKN1A thanCYP24A1mRNA mole-cules are produced after induction with 1a,25(OH)2D3.

[eldarlmario]

Why only TOPICAL calcitirol or Calcipotriol should be used:

Topical applications WILL go systemic- but they will affect hair follicles the balding scalp first before some of it goes into the bloodstream and affect the balding skull to enhance bone resorption.

Oral go both ways but we will all want the hair follciles to be affected first AND this http://en.wikipedia.org/wiki/Vitamin_D-binding_protein is a concern because the scoliosis study stated that VDR has an altered binding site- the above could potentially be the binding sit altered and it might result in calcitirol in the blood stream NOT getting transported to the hair follicles on the balding scalp and http://en.wikipedia.org/wiki/Osteoclast in the balding skull to upregulate CD200 and hence- causing the possible pathologic reason why CD200 is unexpressed in the balding scalp and balding skull.

So to be safe- topical application will be a better option because it bypasses that step and allows calcitirol(hence- CD200) to be delivered directly to the hair follices.

[eldarlmario]

1 potential downside(if any) i can envision from this protocol(Topical Calcitirol+ Leukotriene Antagonists like Singulair aka Montelukast + Crth2 blocker like TM/Seti/Rama?OC)- would be that we might be more susceptible to fungal infections and common ailments like flu, etc- because we are basically weakening our immune system. That is why we want to limit as much of the de-immunising effects to the balding scalp for as much as possible.

And i believe that's how our body intended it to be anyway- a more forgiving immune environment on our heads to let our hair grow in peace while protecting the rest of our entire body with upmost due diligence from invaders.

[eldarlmario]

On Calcitirol:

http://www.medscape.com/viewarticle/776915_3

Thus, VD inhibits the polarization of Th0 cells to either Th1 or -2 cells(inhibits both TH1 and Th2 production) and simultaneously facilitates the converison of naive Th0 cells to Tregs ones, which protect the organism from autoimmune diseases(promotes t cell differentiation to Regulatory t cells instead) (vide supra). Therefore, it is not surprising that Cantorna et al. have found the number of TGF-? transcripts multiplied upon treating mice with D3 simultaneously with blockade of experimentally induced encephalomyelitis.[112] Evidently, the ratio of differentiation of naive T0 cells to Th1 or Treg cells has tremendous clinical significance[113 - 117] since, as discussed above, the formers induce autoimmune disease, while the latter (Treg cells) exert their tolerogenic action by reducing the production of IL-2, as discussed above. Also, the transcription factor Foxp3 and the above mentioned CTL-4 are involved in this process since the inactivation of the latter factor abolishes the tolerogenic action of Tregs, downregulation of the MHC class II complexes and costimulatory ligands as B1, B2 and CD40.[87,88,113 - 117] Interestingly, one of the latter groups found the IL-4, -5, -13 and IFN-? levels decreased during allergic inflammation upon VD treatment.(Calcitirol treatment decreased il-4(the 'master' cytokine in charge of differentiating other cytokines in the TH2 type . Not to be confused with GATA3- who is the master regulator)[113]

As for the regulatory, that is, tolerogenic T cells, it is important that the 'immunomodulant'[118] VDR favors the differentiation to 'tolerogenic' Tregs, more precisely to CD4+ CD25+ Fox3+ cells producing mainly IL-10, TGF-? but less NF-?B and AP-1 than other T cells.[93,119] Infact, VD also upregulates the expression of CTLA-4 and Foxp3 more exactly CD4+ CD25+ Fox3+ cells.[80] Finally, it is probably worth mentioning that VDR shifts the balance of Th1 versus -2 cells toward the latter(that was the common consensus reached by other studies too). This fact is amply proven by the clinical findings discussed in the second part of the review and some experimental data (vide infra). Nevertheless, this phenomenon does not seem to be quite evident, since VDR inhibits the activity of both the Th1 and -2 cells as discussed below.(This study found that consensus to be contrary) It might probably be explained by the radical reduction of Th1-type cells (vide infra), which under physiological conditions tonically inhibit the Th2 cells, that is, the altered balance might be due to desinhition of Th2 cells.

[eldarlmario]

The sum of these events might result in the enhancement of certain Th2 cell functions, that is, an enhanced propensity toward asthma, allergy, eczema and related disorders at least under experimental conditions,[131] but as discussed in the next part of this review, under clinical conditions VD rather suppresses the atopic disorders.(Calcitirol suppresses TH2-mediated immune responses instead of promoting it. Taken in context- this means it suppresses the majority of immune responses in AGA)

According to several early studies in human T lymphocytes, VD inhibits the production of IgM and IgE(pro-inflammatory Immunogoblin B cells in the blood that mediates allergy responses) by the B cells,[132 - 134] though VD upregulates the GATA-3[135] one of the main transcription factors of Th2 cells. It is tempting to use these experimental findings for interpretation of clinical findings but these studies have not been either repeated or confirmed during the last 20 years.

Further immune effects of calcitriol include suppression of T lymphocyte proliferation in humans,[129] presumably by inhibition of IL-2 production, inhibition of B-cell proliferation and antibody production by them in humans and animals,[40,134 - 136] and inhibition of chemokine-mediated migration and homing (into the lymph nodes) of naive and effector CD4+ T cells and macrophages due to blocking upregulation of E selectin ligands.[136 - 138]

A final earlier neglected point is inhibition by VD Th17 cells and IL-17 production. IL-17 as a newly described cytokine was isolated from TCR-C4-CD8- mouse thymocytes by Kennedy et al.[139] still in 1996, but its physiological and pathological significance has been recognized only a decade later. The IL-17-producing CD4+ cells are termed Th17 cells and are considered pathogenic.[140 - 144] Discussed above, Th17 cells are cytotoxic like the Th1 cells but this lineage is not identical to previously known lineages.[140,141,144] The mature Th17 cells are not suppressed by either Th1 or Th2 cytokines and they are independent of the transcription factors of the former T cells.[140] The development of these Th17 cells is inhibited by both IFN-? and IL-4.[140] In one study, the Th1 pathway antagonized the Th17 one[135] but this work has not yet been confirmed. In mice, Treg cells inhibit Th17 cell responses by IL-10.[145] Thus, Th1 and -17 represent different lineages, but their physiological functions are similar and both are antagonized by Treg cells.[140] That is, Treg cells might be physiological antagonists of both subsets of cytotoxic T cells.

[eldarlmario]

btw a trivial:

This seems to fit the theory of those who preach that AGA is atually a condition induced by bacteria on the scalp:

http://en.wikipedia.org/wiki/Cathelicidin

[eldarlmario]

Now as for VD, IL-17 enhances the expression of cathelicidin in human keratinocytes but only in the presence of this vitamin. Otherwise according to some very recent studies, VD also inhibits the Th17-mediated immune functions.[86,155,156] Chang et al. found that in mice, VD inhibited the expression of IL-17 at the level of translation, more precisely via enhanced expression of C/EBP homologous proteins known to inhibit the process of translation and ameliorated experimental encephalomyelitis.[155] VD also inhibits experimental autoimune uveitis by suppressing TH17 polarization.[156] In another study made on stimulated peripheral blood mononuclear cells taken from patients in the early stage of rheumatoid arthritis, VD inhibited the expression of IL-17A, IFN-? and IL-4.[157] VD combined with vitamin A blocked the expression of IL-17 and -23 in both naive and in human CD4+ memory cells.[158] The physiological significance of these findings is proven by the study of Bruce et al. who found that in VDR knockout mice, the number of Th17 cells was higher and the experimentally induced bowel disease was aggravated.[159](in summary- Cacitirol suppresses Th17-mediated autoimmune responses too)

[eldarlmario]

Epidemiological & Genetic Data

Acccording to some recent studies and meta-analyses, serum VD level is reduced in asthma patients and in other diseases accompanied with reduced FEV1, for example, according to the meta-analysis of Paul et al., in the USA 61% of young asthmatics have VD deficiency.[183] Nevertheless, they concluded that "VD supplementation as a preventive or secondary treatment is advisable and must await results of ongoing trials...".[183] Recently, Morales et al. reported that higher maternal circulating VD concentrations were associated with a lower risk of respiratory tract infection in childhood but not with less wheezing and asthma.[184] Thus, the etiological role of VD is not fully proven. However, two groups noted recently that low serum VD level in asthma was associated with impaired lung function, FEV1, airway hyperresponsiveness and reduced therapeutic efficacy of inhaled corticosteroids.[185,186] Wjst et al. came to the conclusion that in spite of the significant influence of external factors such as dietary intake and exposure to sunshine, the serum 25-OH-D3 (calcitriol) level seems to be a heritable trait in families with asthma.[45] Their conclusion was confirmed by several other groups.[28,187] Thus, VD hypovitaminosis is really an etiological factor in asthma, which is, however, also dependent on genetic disposition. Therefore, VD supplementation is apparently at the threshold of becoming a standard component of asthma prevention and its secondary/adjunct treatment as put forward by Majak et al..[185] Nevertheless, the situation is complicated by several further confounding factors:

Low VD serum level is associated with increased airway smooth muscle mass, which is not secondary to asthmatic inflammation, nevertheless it may aggravate the eventually coexisting asthma;[188,189]

Solar exposure in the vicinity of the equator might be beneficial for increasing the synthesis of VD but the same climate per se favors to allergic sensitization;[190,191]

VD as an overall immunosuppressant agent might be favorable in asthma treatment but the shift of the Th1/2 balance toward the latter could facilitate the development of asthma;

Both too low and too high VD levels have been found to enhance sensitization to aeroallergens;[191]

Finally, an unexplained finding that in the brochoalvelar lavage, but not in the serum, the level of VD binding protein is particularly high in severe therapy-resistant asthma.[192]

If VD is really linked to the genesis of asthma, the eventual polymorphism of the VDR gene is expected to be associated with the prevalence of asthma. In most related studies, the polymorphism of the VDR gene was examined by restriction enzymes (Bsml, Apal, TaqI and so on).[193] In some studies, the polymorphism of genes coding for the enzymes involved in the synthesis of VD[8,194] has been observed. Certain variants identified by restriction length polymorphism of VDR showed statistically significant but modest correlation with the prevalence of asthma.[195 - 199] Wjst et al. found a single-base variation in the VDR gene upon comparing asthmatic and their unaffected siblings.[198] Thus, they concluded that VDR exerts protective action against asthma. As mentioned above, the genetic polymorphism of VD binding protein in the plasma has been linked to airway diseases.[200] Others detected gene variants expressed in human activated NKT cells or CD8+ lymphocytes.[197] Finally, in a recent study by Bener et al., they found that more than a third of the asthmatic children had positive familial history of asthma and/or VD deficiency.[201] Truly in an earlier work[202] the VDR gene was found associated with asthma. Probably in this earlier work the technique used was not sophisticated enough. (In summary- Vitamin D deficiency could be the pathological cause of asthma AND AGA because we ARE having 'asthma of the balding scalp. Rememeber- CRTH2 inhibitors are originally designed for asthma and the 'allergen' in AGA is sadly- our hair follicles.'

and the study goes on and on and on(9 pages long)

So please ready the study yourself and i will just post the conclusion of this study:

Five-year View
It can be hoped that the public health significance of undiagnosed VD hyopvitaminosis(suggesting that pathology of AGA could be due to a lack of Cacitirol-activated Cacitirol Receptor levels on the balding scalp) will be finally recognized first by the medical community then by society in general(It might be- Multiple ethinc groups living north of the Equator has a lack of vitamin D levels in their body- not to mention that Vitamin D was only originally classed as a vitamin(the name of it already tells us so) before being reclassed as a critical nuclear hormone that has diverse fucntions in the human body- particularly Calcium homeostasis and the Immune system. Coupled with the fact that the Pax1 gene is in charge of sclerotome planning of the spine and skull, and is also expressed on the adult human scalp- there remains the possibility that variants in the region of the Pax1/foxa2 locus is influencing VDR's function(atually it is indeed doing so by altering VDR's 'binding site'- as indicated by the Scoliosis study)- localized to the balding scalp and skull) Hopefully more and more lay people will understand that VD deficiency is a risk factor of many diseases affecting broad segments of society just as the lack of vitamin C, certain minerals, unhealthy nutrition and so on are detrimental. In an ideal scenario, complaint-free people will be regularly screened not only for hypertension, diabetes and various types of cancer but also for VD hypovitaminosis. Epidemiologists might provide more data on that which factors of living conditions and eating habits contribute to VD hypovitaminosis, which has already reached epidemic proportions.

[eldarlmario]

Guys remember i said i was certain i wasnt really imagining things about this chronic and annoying weird inner ear problem i have. Remember I said i had 1)chronic tinnitus, 2)had a nerve'twisted' in my head whenever i adjust my jaw or moved my neck, 3)inner ear pain:

and i suspect this gene has got to do with it

H6 family homeobox 2 <====Inner ear and vestibular function (altered gene by the Pax1/Foxa2 AGA/Scoliosis haplotype variant)

and i've got a slightly-curved spine diagnosed by my school medical team during my elementary school days.

look what i just found today:

http://immortalhair.forumandco...oulders-are-misaigned

"My left shoulder is higher then my right one(Idiopathic Scoliosis) and it could be the reason maybe why I had this ringing in my right ear(Tinnitus) for 2 years. I did a free chiropractic consultation."

I thought they were BSing me just to say that for me to come in and make some coin, but I look in the mirror and its pretty noticable, had a family member comment on it the same day and I didnt even tell them about the consultation.

Anyone here have any experience with one?



"1)chronic tinnitus, 2)had a nerve'twisted' in my head whenever i adjust my jaw or moved my neck, 3)inner ear pain"

http://www.youtube.com/watch?v=xoml9njNExI

[eldarlmario]

The position of the Atlas influences the entire body

In a chain-reaction process, a misalignment of the Atlas may cause asymmetries of the entire skeleton, such as one shoulder being higher than the other with pain in the scapula, scoliosis, tilted pelvis with consequent danger of herniated discs (discopathy), pain in the back, hips, knees and even feet.

As long as postural defects exist, permanent muscular tension develop which, as well as being painful, can cause other vertebrae in the column to become blocked (subluxations).

The resulting subluxations may create persistent compression on certain nerve roots. More and more frequently doctors use cortisone against those irritations, which is indeed a useful medicament, but which causes severe, well noted side effects in the long term.

Compression of certain nerves (leads to pins and needles) in arms and legs, while the pressure put on other nerves leads to malfunctions in the corresponding organs. This gives rise to a series of disturbances, even in apparently unrelated areas of the body.

Enlarged, hardened muscles as a result of constant tension compress lymphatic structures as well as the arteries and veins which run between these muscles. This leads to decreased blood flow and a build-up of metabolic waste products in the tissue. This condition causes a vicious circle, making the muscles even more rigid.

Certainly, there are other factors to be taken into account which can affect a symmetrical, upright posture of the body. However, misalignment of the Atlas can be absolutely decisive. Experience has shown that in many cases - after a simple correction of the Atlas - the skeleton consequently takes on a more correct and natural shape.

If one shoulder is higher than the other or the pelvis is tilted, complaints are inevitable, sooner or later.

everything is true. that's what i have been complaining about the lymph nodes below my jawline and under my ears for a longtime.

[eldarlmario]

Atlas Verterba:

[eldarlmario]

https://en.wikipedia.org/wiki/Vertebral_artery

[eldarlmario]

The topmost area with the veins coloured in yellow is where im having my lifelong-chronic discomfort that began during puberty Guess where 1 of the blood arteries lead to? Yes- the temples